HELP     Sign In
Search

Relevance to Autism

Recurrent mutations in the SHANK3 gene have been identified in multiple individuals with ASD as described below. SHANK3 lies within a multi-genic region on chromosome 22 that is deleted in Phelan-McDermid syndrome, a disorder which is frequently accompanied by ASD. De novo and inherited point mutations and copy number variants involving SHANK3 have been identified in individuals with ASD in multiple reports (PMIDs 17173049, 17999366, 18615476, 20186804, 20385823, 21378602, 21624971, 22558107, 22892527, 23758760), including de novo SHANK3 variants in PMIDs 17173049, 17999366 and 18615476 that were predicted to be loss-of-function variants or shown experimentally to disrupt SHANK3 function. An additional seven de novo loss-of-function variants in SHANK3 were identified in simplex ASD cases in Leblond et al., 2014 (PMID 25188300); in contrast, no truncating variants in SHANK3 were observed in 1,031 controls. Individuals with truncating SHANK3 variants were found to display ASD with moderate to severe/profound intellectual disability (mean IQ of 31 8) in this report. Furthermore, in a screen and meta-analysis of SHANK copy number variants in ASD, SHANK3 deletions were shown to be statistically enriched in ASD cases compared to controls [10/5,657 cases (0.18%) vs. 2/19,163 controls (0.01); P=0.019, OR=4.05 (1.26-13.01)] (PMID 25188300). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Multiple inconsistent associations have been reported with idiopathic ASD in other studies (PMIDs 19384346, 19566951, 22892527, 24398551, 27876814). De novo SHANK3 mutations in individuals with schizophrenia have also been reported in Gauthier et al., 2010 (PMID 20385823), and association of SHANK3 with schizophrenia has been reported as well (PMID 28371232).

Molecular Function

Shank proteins are multidomain scaffold proteins of the postsynaptic density that connect neurotransmitter receptors, ion channels, and other membrane proteins to the actin cytoskeleton and G-protein-coupled signaling pathways. Shank proteins also play a role in synapse formation and dendritic spine maturation.

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders.
ASD
Positive Association
Learning-dependent chromatin remodeling highlights noncoding regulatory regions linked to autism.
ASD
Positive Association
A genome-wide investigation into parent-of-origin effects in autism spectrum disorder identifies previously associated genes including SHANK3.
ASD
Positive Association
A commonly carried genetic variant, rs9616915, in SHANK3 gene is associated with a reduced risk of autism spectrum disorder: replication in a Chine...
ASD
Negative Association
Analysis of a purported SHANK3 mutation in a boy with autism: clinical impact of rare variant research in neurodevelopmental disabilities.
ASD
Negative Association
Association study of SHANK3 gene polymorphisms with autism in Chinese Han population.
ASD
Negative Association
Copy number variation and association analysis of SHANK3 as a candidate gene for autism in the IMGSAC collection.
ASD
Negative Association
Association between SHANK3 polymorphisms and susceptibility to autism spectrum disorder.
ASD
Negative Association
Lack of association between NLGN3, NLGN4, SHANK2 and SHANK3 gene variants and autism spectrum disorder in a Chinese population.
ASD
Negative Association
Association study of the CNS patterning genes and autism in Han Chinese in Taiwan.
ASD
Support
Genome-wide characteristics of de novo mutations in autism.
ASD
Support
Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing.
ID
Support
Genomic diagnosis for children with intellectual disability and/or developmental delay.
ID
Support
Whole genome sequencing reveals a de novo SHANK3 mutation in familial autism spectrum disorder.
ASD, ID, epilepsy/seizures
Support
Direct measure of the de novo mutation rate in autism and schizophrenia cohorts.
ASD, SCZ
Support
Copy number variation analysis in adults with catatonia confirms haploinsufficiency of SHANK3 as a predisposing factor.
ID, catatonia
Support
Performance comparison of bench-top next generation sequencers using microdroplet PCR-based enrichment for targeted sequencing in patients with aut...
ASD
ID, epilepsy
Support
Neurogenetic analysis of childhood disintegrative disorder.
Childhood disintegrative disorder
Support
Whole-genome sequencing of quartet families with autism spectrum disorder.
ASD
Support
Novel de novo SHANK3 mutation in autistic patients.
ASD
Support
Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability.
ID
Support
Bipolar affective disorder and early dementia onset in a male patient with SHANK3 deletion.
BPD
ID
Support
Investigation of SHANK3 in schizophrenia.
SCZ
Support
Large-scale discovery of novel genetic causes of developmental disorders.
DD
Speech delay
Support
Contribution of SHANK3 mutations to autism spectrum disorder.
ASD
Support
Targeted resequencing of 358 candidate genes for autism spectrum disorder in a Chinese cohort reveals diagnostic potential and genotype-phenotype c...
ASD
Support
Gene Mutation Analysis in 253 Chinese Children with Unexplained Epilepsy and Intellectual/Developmental Disabilities.
DD, ID, epilepsy/seizures
Support
High-throughput sequencing of mGluR signaling pathway genes reveals enrichment of rare variants in autism.
Non-syndromic ASD
Support
SHANK proteins limit integrin activation by directly interacting with Rap1 andR-Ras.
Support
Recurrent de novo mutations implicate novel genes underlying simplex autism risk.
ASD
Support
Genetic Diagnostic Evaluation of Trio-Based Whole Exome Sequencing Among Children With Diagnosed or Suspected Autism Spectrum Disorder.
ASD
DD/ID
Support
Case report: an unexpected link between partial deletion of the SHANK3 gene and Heller's dementia infantilis, a rare subtype of autism spectrum dis...
Childhood disintegrative disorder
Developmental regression
Support
Oligogenic heterozygosity in individuals with high-functioning autism spectrum disorders.
ASD
Support
Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.
ASD
Support
Synaptic, transcriptional and chromatin genes disrupted in autism.
ASD
Support
Two de novo novel mutations in one SHANK3 allele in a patient with autism and moderate intellectual disability.
ASD, ID
Support
Phenotypic and functional analysis of SHANK3 stop mutations identified in individuals with ASD and/or ID.
ASD, ID
Support
SHANK3 mutations identified in autism lead to modification of dendritic spine morphology via an actin-dependent mechanism.
Support
The spectrum of epilepsy and electroencephalographic abnormalities due to SHANK3 loss-of-function mutations.
Epilepsy/seizures
Support
Refining analyses of copy number variation identifies specific genes associated with developmental delay.
ASD, DD, ID
Support
Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder.
ASD
Support
De novo SHANK3 mutation causes Rett syndrome-like phenotype in a female patient.
Rett syndrome-like phenotype
DD, autistic features, stereotyped hand movements,
Support
Novel variants of the SHANK3 gene in Japanese autistic patients with severe delayed speech development.
ASD
Highly Cited
Proline-rich synapse-associated proteins ProSAP1 and ProSAP2 interact with synaptic proteins of the SAPAP/GKAP family.
Recent Recommendation
Autism-Associated Insertion Mutation (InsG) of Shank3 Exon 21 Causes Impaired Synaptic Transmission and Behavioral Deficits.
Recent Recommendation
22q13.3 deletion syndrome: clinical and molecular analysis using array CGH.
Phelan-McDermid syndrome
MR
Recent Recommendation
Altered spinogenesis in iPSC-derived cortical neurons from patients with autism carrying de novo SHANK3 mutations.
Recent Recommendation
SHANK3 gene mutations associated with autism facilitate ligand binding to the Shank3 ankyrin repeat region.
ASD
Recent Recommendation
An architectural framework that may lie at the core of the postsynaptic density.
Recent Recommendation
Two knockdown models of the autism genes SYNGAP1 and SHANK3 in zebrafish produce similar behavioral phenotypes associated with embryonic disruption...
Recent Recommendation
Synaptic cross-talk between N-methyl-D-aspartate receptors and LAPSER1-beta-catenin at excitatory synapses.
Recent Recommendation
An autism-linked missense mutation in SHANK3 reveals the modularity of Shank3 function.
ASD
Recent Recommendation
Prospective investigation of autism and genotype-phenotype correlations in 22q13 deletion syndrome and SHANK3 deficiency.
ASD
ID, epilepsy/seizures
Recent Recommendation
Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: a gradient of severity in cognitive impairments.
ASD
Recent Recommendation
Disruption of glutamate receptors at Shank-postsynaptic platform in Alzheimer's disease.
Recent Recommendation
Delineation of the genetic and clinical spectrum of Phelan-McDermid syndrome caused by SHANK3 point mutations.
Phelan-McDermid syndrome
ASD
Recent Recommendation
Shank3-Rich2 interaction regulates AMPA receptor recycling and synaptic long-term potentiation.
Recent Recommendation
Transcriptional and functional complexity of Shank3 provides a molecular framework to understand the phenotypic heterogeneity of SHANK3 causing aut...
Recent Recommendation
ProSAPiP2, a novel postsynaptic density protein that interacts with ProSAP2/Shank3.
Recent Recommendation
Shank3 Is Part of a Zinc-Sensitive Signaling System That Regulates Excitatory Synaptic Strength.
Recent Recommendation
Prevalence of SHANK3 variants in patients with different subtypes of autism spectrum disorders.
ASD
Recent Recommendation
The PSD protein ProSAP2/Shank3 displays synapto-nuclear shuttling which is deregulated in a schizophrenia-associated mutation.
Recent Recommendation
Chromosome 22q13.3 deletion syndrome with a de novo interstitial 22q13.3 cryptic deletion disrupting SHANK3.
ID
Recent Recommendation
Autism-associated SHANK3 haploinsufficiency causes Ih channelopathy in human neurons.
Recent Recommendation
Shank3 mutant mice display autistic-like behaviours and striatal dysfunction.
Recent Recommendation
Epigenetic dysregulation of SHANK3 in brain tissues from individuals with autism spectrum disorders.
Recent Recommendation
Heterogeneous dysregulation of microRNAs across the autism spectrum.
Recent Recommendation
Low load for disruptive mutations in autism genes and their biased transmission.
ASD
Recent Recommendation
De novo mutations in the gene encoding the synaptic scaffolding protein SHANK3 in patients ascertained for schizophrenia.
SCZ
Recent Recommendation
Shank3 deficiency induces NMDA receptor hypofunction via an actin-dependent mechanism.
Recent Recommendation
Smaller dendritic spines, weaker synaptic transmission, but enhanced spatial learning in mice lacking Shank1.

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN230R001 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R002 
 frameshift_variant 
 c.3680insG 
 p.Ala1227Glyfs 
 De novo 
  
 Multiplex 
 GEN230R003 
 copy_number_loss 
  
  
  
  
  
 GEN230R004 
 copy_number_gain 
  
  
  
  
  
 GEN230R005 
 missense_variant 
 c.34C>T 
 p.Arg12Cys 
 Familial 
 Maternal 
 Multiplex 
 GEN230R006 
 missense_variant 
 c.593C>G 
 p.Ala198Gly 
 Familial 
 Maternal 
 Multiplex 
 GEN230R007 
 missense_variant 
 c.898C>T 
 p.Arg300Cys 
 Familial 
 Maternal 
 Simplex 
 GEN230R008 
 missense_variant 
 c.3032G>T 
 p.Gly1011Val 
 Familial 
  
 Unknown 
 GEN230R009 
 missense_variant 
  
 p.Arg1066Leu 
 Familial 
 Maternal 
 Simplex 
 GEN230R010 
 missense_variant 
 c.3692G>A 
 p.Arg1231His 
 Familial 
 Maternal 
 Multiplex 
 GEN230R011 
 missense_variant 
  
 p.Ser1566Gly 
 Familial 
 Paternal 
 Simplex 
 GEN230R012 
 stop_gained 
 c.3349C>T 
 p.Arg1117Ter 
 De novo 
  
 Multiplex 
 GEN230R013 
 missense_variant 
 c.1606C>T 
 p.Arg536Trp 
 De novo 
  
  
 GEN230R014 
 synonymous_variant 
 c.1023G>A 
 p.(=) 
  
  
  
 GEN230R015 
 missense_variant 
 c.1479C>G 
 p.His494Gln 
  
  
  
 GEN230R016 
 synonymous_variant 
 c.1893C>T 
 p.(=) 
  
  
  
 GEN230R017 
 synonymous_variant 
 c.2043C>G 
 p.(=) 
  
  
  
 GEN230R018 
 missense_variant 
 c.2856G>C 
 p.Ser952Thr 
  
  
  
 GEN230R019 
 missense_variant 
 c.3032G>T 
 p.Gly1011Val 
  
  
  
 GEN230R020 
 synonymous_variant 
 c.3066G>A 
 p.(=) 
  
  
  
 GEN230R021 
 missense_variant 
 c.3401C>A 
 p.Pro1134His 
  
  
  
 GEN230R022 
 synonymous_variant 
 c.3482T>C 
 p.(=) 
  
  
  
 GEN230R023 
 synonymous_variant 
 c.3558G>A 
 p.(=) 
  
  
  
 GEN230R024 
 missense_variant 
 c.962A>G 
 p.Gln321Arg 
 De novo 
  
 Simplex 
 GEN230R025 
 missense_variant 
 c.1022C>T 
 p.Ser341Leu 
 Familial 
 Paternal 
 Simplex 
 GEN230R026 
 missense_variant 
 c.2908G>T 
 p.Ala970Ser 
 Familial 
 Paternal 
 Simplex 
 GEN230R027 
 missense_variant 
 c.3517G>A 
 p.Ala1173Thr 
 Familial 
 Maternal 
 Multiplex 
 GEN230R028 
 missense_variant 
 c.3788C>T 
 p.Pro1263Leu 
 Familial 
 Paternal 
 Simplex 
 GEN230R029 
 missense_variant 
 c.4216C>G 
 p.Leu1406Val 
 Familial 
 Maternal 
 Multiplex 
 GEN230R030 
 missense_variant 
 c.4328T>C 
 p.Met1443Thr 
 Familial 
 Maternal 
 Simplex 
 GEN230R031 
 inframe_deletion 
 Del4358-4372 
 Del of 5 aa 
 Familial 
 Maternal 
 Multiplex 
 GEN230R032 
 missense_variant 
 c.4669G>A 
 p.Gly1557Ser 
 Familial 
 Paternal 
 Simplex 
 GEN230R033 
 missense_variant 
 c.4960C>A 
 p.Pro1654Thr 
 Familial 
 Paternal 
 Multiplex 
 GEN230R034 
 missense_variant 
 c.4960C>A 
 p.Pro1654Thr 
 Familial 
 Maternal 
 Multiplex 
 GEN230R035 
 copy_number_loss 
  
  
 De novo 
  
 Simplex 
 GEN230R036 
 copy_number_loss 
  
  
 Familial 
 Paternal 
 Simplex 
 GEN230R037 
 copy_number_loss 
  
  
 De novo 
  
 Multiplex 
 GEN230R038 
 missense_variant 
 c.203T>C 
 p.Leu68Pro 
 Familial 
 Paternal 
 Simplex 
 GEN230R039 
 missense_variant 
 c.670G>A 
 p.Ala224Thr 
 Unknown 
  
 Unknown 
 GEN230R040 
 missense_variant 
 c.2161G>A 
 p.Ala721Thr 
 Unknown 
  
 Unknown 
 GEN230R041 
 splice_site_variant 
 c.2265C+1delG 
 p.Ser755SerfsTer1 
 De novo 
  
 Simplex 
 GEN230R042 
 missense_variant 
 c.3893G>A 
 p.Arg1298Lys 
 Familial 
 Maternal 
  
 GEN230R043 
 missense_variant 
 c.4960C>A 
 p.Pro1654Thr 
 Unknown 
  
 Unknown 
 GEN230R044 
 missense_variant 
 c.734T>C 
 p.Ile245Thr 
 Unknown 
  
 Unknown 
 GEN230R045 
 inframe_deletion 
 c.1320_1338del18 
 p.delGlyProGlyProAlaPro 
 Familial 
 Maternal 
  
 GEN230R046 
 missense_variant 
 c.1967G>A 
 p.Arg656His 
 Familial 
 Paternal 
  
 GEN230R047 
 intron_variant 
 N/A 
 N/A 
  
  
  
 GEN230R048 
 intron_variant 
 N/A 
 N/A 
  
  
  
 GEN230R049 
 intron_variant 
 N/A 
 N/A 
 De novo 
  
  
 GEN230R050 
 copy_number_loss 
  
  
 Familial 
 Maternal 
  
 GEN230R051 
 inframe_insertion 
 N/A 
 N/A 
  
  
  
 GEN230R052 
 missense_variant 
 c.734T>C 
 p.Ile245Thr 
  
  
  
 GEN230R053 
 missense_variant 
 c.3517G>A 
 p.Ala1173Thr 
  
  
  
 GEN230R054 
 missense_variant 
 c.3788G>T 
 p.Pro1263Leu 
  
  
  
 GEN230R055 
 synonymous_variant 
 c.750C>T 
 p.(=) 
  
  
  
 GEN230R056 
 synonymous_variant 
 c.1563G>A 
 p.(=) 
  
  
  
 GEN230R057 
 synonymous_variant 
 c.4446G>A 
 p.(=) 
  
  
  
 GEN230R058 
 synonymous_variant 
 c.4908C>T 
 p.(=) 
  
  
  
 GEN230R059 
 synonymous_variant 
 c.4935C>T 
 p.(=) 
  
  
  
 GEN230R060 
 synonymous_variant 
 c.483C>T 
 p.(=) 
  
  
  
 GEN230R061 
 copy_number_loss 
  
  
 De novo 
  
 Simplex 
 GEN230R062 
 copy_number_loss 
  
  
  
  
  
 GEN230R063 
 copy_number_loss 
  
  
  
  
  
 GEN230R064 
 copy_number_loss 
  
  
  
  
  
 GEN230R065 
 copy_number_loss 
  
  
  
  
  
 GEN230R066 
 copy_number_loss 
  
  
  
  
  
 GEN230R067 
 copy_number_loss 
  
  
  
  
  
 GEN230R068 
 copy_number_loss 
  
  
  
  
  
 GEN230R069 
 copy_number_loss 
  
  
  
  
  
 GEN230R070 
 copy_number_loss 
  
  
  
  
  
 GEN230R071 
 copy_number_loss 
  
  
  
  
  
 GEN230R072 
 copy_number_loss 
  
  
  
  
  
 GEN230R073 
 copy_number_loss 
  
  
  
  
  
 GEN230R074 
 copy_number_loss 
  
  
  
  
  
 GEN230R075 
 missense_variant 
 c.734T>C 
 p.Ile245Thr 
  
  
  
 GEN230R076 
 missense_variant 
 c.2161G>A 
 p.Ala721Thr 
  
  
  
 GEN230R077 
 synonymous_variant 
 c.2310G>A 
 p.(=) 
  
  
  
 GEN230R078 
 synonymous_variant 
 c.2997C>T 
 p.(=) 
  
  
  
 GEN230R079 
 synonymous_variant 
 c.3363C>T 
 p.(=) 
  
  
  
 GEN230R080 
 missense_variant 
 c.3999T>G 
 p.Val1333Gly 
  
  
  
 GEN230R081 
 synonymous_variant 
 c.4947C>T 
 p.(=) 
  
  
  
 GEN230R082 
 missense_variant 
 c.4960C>A 
 p.Pro1654Thr 
  
  
  
 GEN230R083 
 missense_variant 
 c.3581G>A 
 p.Gly1194Asp 
 Unknown 
  
 Simplex 
 GEN230R084 
 missense_variant 
 c.3715A>T 
 p.Ser1239Cys 
 Unknown 
  
 Simplex 
 GEN230R085 
 missense_variant 
 c.3893G>A 
 p.Arg1298Lys 
 Unknown 
  
 Simplex 
 GEN230R086 
 missense_variant 
 c.4018G>A 
 p.Ala1340Thr 
 Unknown 
  
 Simplex 
 GEN230R087 
 missense_variant 
 c.4621C>T 
 p.Pro1541Ser 
 Unknown 
  
 Simplex 
 GEN230R088 
 missense_variant 
 c.4673C>T 
 p.Ala1558Val 
 Unknown 
  
 Simplex 
 GEN230R089 
 missense_variant 
 c.4778A>T 
 p.Thr1593Ile 
 Unknown 
  
 Simplex 
 GEN230R090 
 missense_variant 
 c.4856G>A 
 p.Arg1619His 
 Unknown 
 Not paternal 
 Simplex 
 GEN230R091 
 missense_variant 
 c.4873A>T 
 p.Pro1625Ser 
 Unknown 
  
 Simplex 
 GEN230R092 
 missense_variant 
 c.4877C>T 
 p.Ser1626Lys 
 Unknown 
  
 Simplex 
 GEN230R093 
 missense_variant 
 c.4894G>A 
 p.Ala1632Thr 
 Unknown 
 Not paternal 
 Simplex 
 GEN230R094 
 missense_variant 
 c.4913G>A 
 p.Gly1638Asp 
 Unknown 
  
 Simplex 
 GEN230R095 
 missense_variant 
 c.4960C>A 
 p.Pro1654Thr 
 Unknown 
  
 Simplex 
 GEN230R096 
 synonymous_variant 
 c.522C>T 
 p.(=) 
  
  
 Multiplex 
 GEN230R097 
 missense_variant 
 c.612C>A 
 p.Asp204Glu 
  
  
 Multiplex 
 GEN230R098 
 missense_variant 
 c.763C>T 
 p.His255Tyr 
  
  
 Multiplex 
 GEN230R099 
 intron_variant 
 c.769-7C>G 
  
  
  
 Multiplex 
 GEN230R100 
 missense_variant 
 c.898C>T 
 p.Arg300Cys 
  
  
 Multiplex 
 GEN230R101 
 missense_variant 
 c.920C>G 
 p.Ala307Gly 
  
  
 Multiplex 
 GEN230R102 
 intron_variant 
 c.1031-14C>T 
  
  
  
 Multiplex 
 GEN230R103 
 synonymous_variant 
 c.1254G>A 
 p.(=) 
  
  
 Multiplex 
 GEN230R104 
 missense_variant 
 c.1315C>T 
 p.Pro439Ser 
  
  
 Multiplex 
 GEN230R105 
 synonymous_variant 
 c.1335G>T 
 p.(=) 
  
  
 Multiplex 
 GEN230R106 
 missense_variant 
 c.1337G>T 
 p.Gly446Val 
  
  
 Multiplex 
 GEN230R107 
 intron_variant 
 c.2077+10C>A 
  
  
  
 Multiplex 
 GEN230R108 
 intron_variant 
 c.2313+20G>A 
  
  
  
 Multiplex 
 GEN230R109 
 intron_variant 
 c.2398+11G>A 
  
  
  
 Multiplex 
 GEN230R110 
 synonymous_variant 
 c.249G>T 
 p.(=) 
  
  
 Multiplex 
 GEN230R111 
 synonymous_variant 
 c.3360C>T 
 p.(=) 
  
  
 Multiplex 
 GEN230R112 
 synonymous_variant 
 c.3708G>A 
 p.(=) 
  
  
 Multiplex 
 GEN230R113 
 missense_variant 
 c.3761C>T 
 p.Ala1254Val 
  
  
 Multiplex 
 GEN230R114 
 missense_variant 
 c.3764C>T 
 p.Pro1255Leu 
  
  
 Multiplex 
 GEN230R115 
 synonymous_variant 
 c.3765G>A 
 p.(=) 
  
  
 Multiplex 
 GEN230R116 
 missense_variant 
 c.3836C>T 
 p.Pro1279Leu 
  
  
 Multiplex 
 GEN230R117 
 missense_variant 
 c.4025C>T 
 p.Pro1342Leu 
  
  
 Multiplex 
 GEN230R118 
 synonymous_variant 
 c.4050C>T 
 p.(=) 
  
  
 Multiplex 
 GEN230R119 
 synonymous_variant 
 c.4368C>T 
 p.(=) 
  
  
 Multiplex 
 GEN230R120 
 missense_variant 
 c.4405G>C 
 p.Gly1469Arg 
  
  
 Multiplex 
 GEN230R121 
 missense_variant 
 c.4406G>T 
 p.Gly1469Val 
  
  
 Multiplex 
 GEN230R122 
 synonymous_variant 
 c.4479C>T 
 p.(=) 
  
  
 Multiplex 
 GEN230R123 
 missense_variant 
 c.4490G>A 
 p.Arg1497Gln 
  
  
 Multiplex 
 GEN230R124 
 synonymous_variant 
 c.4641C>T 
 p.(=) 
  
  
 Multiplex 
 GEN230R125 
 missense_variant 
 c.4720G>A 
 p.Gly1574Arg 
  
  
 Multiplex 
 GEN230R126 
 synonymous_variant 
 c.5106C>T 
 p.(=) 
  
  
 Multiplex 
 GEN230R127 
 splice_site_variant 
 del(G) 
 Splice-site 
 De novo 
  
  
 GEN230R128 
 missense_variant 
 c.1606C>T 
 p.Arg536Trp 
 De novo 
  
  
 GEN230R129 
 stop_gained 
 c.3349C>T 
 p.Arg1117Ter 
 De novo 
  
  
 GEN230R130 
 frameshift_variant 
 c.1339_1340insG 
 p.Ala447GlyfsTer57 
 Familial 
 Maternal 
  
 GEN230R131 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R132 
 frameshift_variant 
 c.1339_1340insG 
 p.Ala447fsTer503 
 Familial 
 Paternal 
 Possible multi-generational 
 GEN230R133 
 frameshift_variant 
 c.3931delG 
 p.Glu1311fsTer1401 
 Unknown (not maternal) 
  
  
 GEN230R134 
 missense_variant 
 c.421C>G 
 p.Pro141Ala 
 De novo 
  
  
 GEN230R135 
 splice_site_variant 
 c.1820-4G>A 
  
 Familial 
 Maternal 
  
 GEN230R136 
 missense_variant 
 c.4402G>T 
 p.Ala1468Ser 
 Unknown 
  
  
 GEN230R137 
 copy_number_loss 
  
  
 De novo 
  
 Simplex 
 GEN230R138 
 copy_number_loss 
  
  
 Unknown (not maternal) 
  
  
 GEN230R139 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R140 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R141 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R142 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R143 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R144 
 copy_number_loss 
  
  
 Unknown (not maternal) 
  
  
 GEN230R145 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R146 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R147 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R148 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R149 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R150 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R151 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R152 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R153 
 copy_number_loss 
  
  
 Unknown (not paternal) 
  
  
 GEN230R154 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R155 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R156 
 copy_number_loss 
  
  
 Unknown (not paternal) 
  
  
 GEN230R157 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R158 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R159 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R160 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R161 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R162 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R163 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R164 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R165 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R166 
 copy_number_loss 
  
  
 Unknown (not paternal) 
  
  
 GEN230R167 
 copy_number_loss 
  
  
 Unknown (not maternal) 
  
  
 GEN230R168 
 frameshift_variant 
 c.2497delG 
 p.Pro834ArgfsTer59 
 De novo 
  
  
 GEN230R169 
 stop_gained 
 c.1527G>A 
 p.Trp509Ter 
 De novo 
  
  
 GEN230R170 
 missense_variant 
 c.3169C>T 
 p.Leu1057Phe 
 Unknown 
  
 Unknown 
 GEN230R171 
 stop_gained 
 c.2425G>T 
 p.Glu809Ter 
 De novo 
  
 Simplex 
 GEN230R172 
 frameshift_variant 
 delCCCTG 
 p.Ala1076GlufsTer218 
 De novo 
  
 Simplex 
 GEN230R173 
 frameshift_variant 
 delCT 
 p.Leu1142ValfsTer153 
 De novo 
  
 Simplex 
 GEN230R174 
 frameshift_variant 
 delCCCT 
 p.Ser1202CysfsTer81 
 De novo 
  
 Simplex 
 GEN230R175 
 frameshift_variant 
 delGGGCCCAGCCCCC 
 p.Arg1255LeufsTer25 
 De novo 
  
 Simplex 
 GEN230R176 
 frameshift_variant 
 insGGCCA 
 p.Gly1271AlafsTer15 
 De novo 
  
 Simplex 
 GEN230R177 
 stop_gained 
 c.3727C>T 
 p.Gln1243Ter 
 De novo 
  
 Simplex 
 GEN230R178 
 frameshift_variant 
 delC 
 p.Pro1005ArgfsTer73 
 Unknown 
 Not maternal 
 Simplex 
 GEN230R179 
 frameshift_variant 
 delAG 
 p.Gly1339GlufsTer5 
 Unknown 
 Not maternal 
 Simplex 
 GEN230R180 
 inframe_deletion 
 delCCCGGCCCCGCG 
 p.Pro442_Ala445del 
 Unknown 
  
 Unknown 
 GEN230R181 
 missense_variant 
 c.1682C>T 
 p.Ser561Leu 
 Unknown 
  
 Unknown 
 GEN230R182 
 missense_variant 
 c.2254G>A 
 p.Ala752Thr 
 Unknown 
  
 Unknown 
 GEN230R183 
 missense_variant 
 c.2685T>C 
 p.Leu895Pro 
 Unknown 
  
 Unknown 
 GEN230R184 
 missense_variant 
 c.3032G>T 
 p.Gly1011Val 
 Unknown 
  
 Unknown 
 GEN230R185 
 missense_variant 
 c.3704C>A 
 p.Pro1235Gln 
 Unknown 
  
 Unknown 
 GEN230R186 
 missense_variant 
 c.3796G>A 
 p.Ala1266Thr 
 Unknown 
  
 Unknown 
 GEN230R187 
 missense_variant 
 c.3825A>T 
 p.Glu1275Asp 
 Unknown 
  
 Unknown 
 GEN230R188 
 copy_number_loss 
  
  
 De novo 
  
 Simplex 
 GEN230R189 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R190 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R191 
 stop_gained 
 c.1485G>A 
 p.Trp495Ter 
 De novo 
  
 Simplex 
 GEN230R192 
 frameshift_variant 
 c.1834_1835insGG 
 p.Thr612fs 
 Familial 
 Paternal 
 Multiplex 
 GEN230R193 
 missense_variant 
 c.2027G>A 
 p.Arg676His 
 Familial 
 Paternal 
 Simplex 
 GEN230R194 
 missense_variant 
 c.3866C>T 
 p.Pro1289Leu 
 Familial 
 Maternal 
 Simplex 
 GEN230R195 
 missense_variant 
 c.3869C>T 
 p.Ala1290Val 
 Familial 
 Maternal 
 Simplex 
 GEN230R196 
 stop_gained 
 c.1575C>A 
 p.Cys525Ter 
 Unknown 
  
 Unknown 
 GEN230R197 
 missense_variant 
 c.920C>G 
 p.Ala307Gly 
 Unknown 
  
 Unknown 
 GEN230R198 
 missense_variant 
 c.985T>A 
 p.Phe329Ile 
 Unknown 
  
 Unknown 
 GEN230R199 
 missense_variant 
 c.2024G>A 
 p.Arg675Gln 
 Unknown 
  
 Unknown 
 GEN230R200 
 missense_variant 
 c.4391G>A 
 p.Arg1464His 
 Unknown 
  
 Unknown 
 GEN230R201 
 missense_variant 
 c.2060G>T 
 p.Ser687Ile 
 Unknown 
  
 Unknown 
 GEN230R202 
 copy_number_loss 
  
  
 Unknown 
  
 Unknown 
 GEN230R203 
 copy_number_loss 
  
  
 De novo 
  
 Simplex 
 GEN230R204 
 frameshift_variant 
 c.925_926delAG 
 p.Arg309GlyfsTer21 
 De novo 
  
 Multiplex 
 GEN230R205 
 frameshift_variant 
 c.3259delC 
 p.Ser1088ProfsTer6 
 De novo 
  
 Multiplex 
 GEN230R206 
 frameshift_variant 
 c.2955_2970dup 
 p.Pro992ArgfsTer325 
 De novo 
  
 Simplex 
 GEN230R207 
 frameshift_variant 
 c.3100delC 
 p.Ala1034fsTer44 
 De novo 
  
 Simplex 
 GEN230R208 
 stop_gained 
 c.5008A>T 
 p.Lys1670Ter 
 Unknown 
 Not maternal 
  
 GEN230R209 
 copy_number_loss 
  
  
 Unknown 
 Not maternal 
  
 GEN230R210 
 missense_variant 
 c.3598G>C 
 p.Ala1200Pro 
 De novo 
  
 Simplex 
 GEN230R211 
 frameshift_variant 
 c.3727dup 
 p.Ala1243fs 
 De novo 
  
  
 GEN230R212 
 frameshift_variant 
 c.4491dupG 
 p.Leu1497fs 
 De novo 
  
 Simplex 
 GEN230R213 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN230R214 
 copy_number_loss 
  
  
 Unknown 
  
  
 GEN230R215 
 splice_site_variant 
 G>A 
 p.? 
 De novo 
  
 Simplex 
 GEN230R216 
 missense_variant 
 c.962A>G 
 p.Gln321Arg 
 De novo 
  
 Simplex 
 GEN230R217 
 frameshift_variant 
 c.2808dupC 
 p.Arg936fs 
 Unknown 
  
 Simplex 
 GEN230R218 
 frameshift_variant 
 delG 
  
 De novo (mosaic) 
  
 Multiplex 
 GEN230R219 
 missense_variant 
 c.484G>A 
 p.Ala162Thr 
 Unknown 
  
  
 GEN230R220 
 missense_variant 
 c.3032G>T 
 p.Gly1011Val 
 Unknown 
  
  
 GEN230R221 
 missense_variant 
 c.3067C>T 
 p.Arg1023Trp 
 Unknown 
  
  
 GEN230R222 
 missense_variant 
 c.3179C>G 
 p.Thr1060Ser 
 Unknown 
  
  
 GEN230R223 
 missense_variant 
 c.3568G>A 
 p.Asp1190Asn 
 Unknown 
  
  
 GEN230R224 
 missense_variant 
 c.3764G>A 
 p.Arg1255Gln 
 Unknown 
  
  
 GEN230R225 
 missense_variant 
 c.4385G>T 
 p.Arg1462Leu 
 Unknown 
  
  
 GEN230R226 
 missense_variant 
 c.4954G>A 
 p.Gly1652Ser 
 Unknown 
  
  
 GEN230R227 
 synonymous_variant 
 c.2889G>C 
 p.(=) 
 Unknown 
  
  
 GEN230R228 
 synonymous_variant 
 c.4947C>T 
 p.(=) 
 Unknown 
  
  
 GEN230R229 
 intron_variant 
 c.63+148G>A 
  
 Unknown 
  
  
 GEN230R230 
 3_prime_UTR_variant 
 c.*27C>T 
  
 Unknown 
  
  
 GEN230R231 
 missense_variant;missense_variant 
 G>A 
 p.[Gly277Arg];[Gly277Arg] 
 Familial 
 Both parents 
 Simplex 
 GEN230R232 
 missense_variant 
 c.1010C>G 
 p.Thr337Ser 
 De novo 
  
  
 GEN230R233 
 missense_variant 
 C>G 
 p.Arg1271Gly 
 De novo 
  
  
 GEN230R234 
 frameshift_variant;missense_variant 
 c.[2860dupC;3236C>T] 
 p.[Leu954Profs342;Pro1079Leu] 
 De novo 
  
  
 GEN230R235 
 frameshift_variant 
 c.2471delC 
 p.Pro824ArgfsTer69 
 De novo 
  
  
 GEN230R236 
 frameshift_variant 
 c.2946_2949delCCGC 
 p.Arg983SerfsTer94 
 De novo 
  
  
 GEN230R237 
 frameshift_variant 
 c.3095_3107delTGGGGGCCATCGA 
 p.Val1032GlyfsTer42 
 De novo 
  
  
 GEN230R238 
 frameshift_variant 
 c.3424_3425delCT 
 p.Leu1142ValfsTer153 
 De novo 
  
  
 GEN230R239 
 frameshift_variant 
 c.3679dupG 
 p.Ala1227GlyfsTer69 
 Unknown 
 Not paternal 
  
 GEN230R240 
 frameshift_variant 
 c.3679dupG 
 p.Ala1227GlyfsTer69 
 De novo 
  
  
 GEN230R241 
 frameshift_variant 
 c.3679dupG 
 p.Ala1227GlyfsTer69 
 De novo 
  
  
 GEN230R242 
 frameshift_variant 
 c.3764_3776delGGGCCCAGCCCCC 
 p.Arg1255LeufsTer25 
 De novo 
  
  
 GEN230R243 
 frameshift_variant 
 c.4065_4066delTG 
 p.Val1357GlyfsTer4 
 De novo 
  
 Multiplex (monozygotic twins) 
 GEN230R244 
 frameshift_variant 
 c.4229delC 
 p.Pro1410HisfsTer18 
 De novo 
  
  
 GEN230R245 
 frameshift_variant 
 c.4577_4578delCC 
 p.Ala1526GlufsTer16 
 De novo 
  
  
 GEN230R246 
 frameshift_variant 
 c.4906_4921dupTCCCCCTCGCCGTCGC 
 p.Pro1641LeufsTer58 
 De novo 
  
  
 GEN230R247 
 missense_variant 
 c.5014G>T 
 p.Asp1672Tyr 
 De novo 
  
  
 GEN230R248 
 missense_variant 
 c.3637A>G 
 p.Ser1213Gly 
 De novo 
  
 Simplex 
 GEN230R249 
 frameshift_variant 
 c.3630dupG 
 p.Leu1210fs 
 De novo 
  
 Simplex 
 GEN230R250 
 frameshift_variant 
 c.3424_3425del 
 p.Leu1142fs 
 De novo 
  
  
 GEN230R251 
 frameshift_variant 
 c.3679dupG 
 p.Ala1227fs 
 Unknown 
  
 Multi-generational 
 GEN230R252 
 frameshift_variant 
 c.3679dupG 
 p.Ala1227fs 
 De novo 
  
  
 GEN230R253 
 missense_variant 
 c.593C>G 
 p.Ala198Gly 
 Unknown 
  
  
 GEN230R254 
 missense_variant 
 c.898C>T 
 p.Pro300Ser 
 Unknown 
  
  

Common

Variant ID
Polymorphism
SNP ID
Allele Change
Residue Change
Population Origin
Population Stage
Author, Year
 GEN230C001 
 intron_variant 
 rs76224556 
 c.1304+48C>T 
  
 Case cohort of 221 ASD patients (133 from South Caroline Autism Project/SCAP, 88 from Italy); control cohort of 982 individuals 
 Discovery 
 GEN230C002 
 missense_variant 
 rs9616915 
 c.734T>C 
 p.Ile245Thr 
 Case cohort of 212 ASD patients; control cohort of 636 controls (Chinese) 
 Discovery 
 GEN230C003 
 intron_variant 
 rs5770820 
 c.2134+407G>A 
  
 Simons Simplex Collection (SSC) GWAS dataset consisting of 2591 simplex ASD families 
 Discovery 
 GEN230C004 
 intron_variant 
 rs140201628 
 c.886-60C>G 
  
 Discovery: 500 German schizophrenia cases (273 males, 227 females, mean age at inclusion=34.4 11 years), 4300 European controls from the Exome Variant Server 
 Discovery 
 GEN230C005 
 intron_variant 
 rs1557620 
 c.1612+18T>C 
  
 Discovery: 500 German schizophrenia cases (273 males, 227 females, mean age at inclusion=34.4 11 years), 503 European controls from the 1000 Genomes Project, and 4300 European controls from the Exome Variant Server 
 Discovery 
 GEN230C006 
 synonymous_variant 
 rs147941361 
 c.1797G>A 
 p.(=) 
 Discovery: 500 German schizophrenia cases (273 males, 227 females, mean age at inclusion=34.4 11 years), 4300 European controls from the Exome Variant Server 
 Discovery 
 GEN230C007 
 missense_variant 
 rs61729471 
 c.2161G>A 
 p.Ala721Thr 
 Discovery: 500 German schizophrenia cases (273 males, 227 females, mean age at inclusion=34.4 11 years), 503 European controls from the 1000 Genomes Project, and 4300 European controls from the Exome Variant Server 
 Discovery 
 GEN230C008 
 synonymous_variant 
 rs557669600 
 c.4947C>T 
 p.(=) 
 Discovery: 500 German schizophrenia cases (273 males, 227 females, mean age at inclusion=34.4 11 years), 503 European controls from the 1000 Genomes Project, and 4300 European controls from the Exome Variant Server 
 Discovery 
 GEN230C009 
 intron_variant 
 rs6010065 
 c.2351-595G>C 
  
 422 ASD cases and 182 typically-developing controls (CHOP) 
 Discovery 
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
22
Duplication
 1
 
22
Duplication
 1
 
22
Deletion-Duplication
 9
 
22
Deletion
 1
 
22
Deletion-Duplication
 16
 
22
Deletion-Duplication
 21
 
22
Duplication
 24
 
22
Deletion-Duplication
 54
 

Model Summary

Specific deficits in synaptic function and plasticity, along with reduced reciprocal social interactions in Shank3 heterozygous mice.

References

Type
Title
Author, Year
Primary
Haploinsufficiency of the autism-associated Shank3 gene leads to deficits in synaptic function, social interaction, and social communication.
Additional
Shank3 mutant mice display autistic-like behaviours and striatal dysfunction.
Additional
Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3.
Additional
Enhanced polyubiquitination of Shank3 and NMDA receptor in a mouse model of autism.
Additional
Autistic-like behaviours and hyperactivity in mice lacking ProSAP1/Shank2.
Additional
Insulin-like growth factor-1 rescues synaptic and motor deficits in a mouse model of autism and developmental delay.
Additional
Loss of predominant Shank3 isoforms results in hippocampus-dependent impairments in behavior and synaptic transmission.
Additional
Autism-like Deficits in Shank3-Deficient Mice Are Rescued by Targeting Actin Regulators.
Additional
Autism-Associated Insertion Mutation (InsG) of Shank3 Exon 21 Causes Impaired Synaptic Transmission and Behavioral Deficits.
Additional
Cerebellar associative sensory learning defects in five mouse autism models.
Additional
Altered Striatal Synaptic Function and Abnormal Behaviour in Shank3 Exon4-9 Deletion Mouse Model of Autism.
Additional
Mice with Shank3 Mutations Associated with ASD and Schizophrenia Display Both Shared and Distinct Defects.
Additional
CLK2 inhibition ameliorates autistic features associated with SHANK3 deficiency.
Additional
Adult restoration of Shank3 expression rescues selective autistic-like phenotypes.
Additional
Altered mGluR5-Homer scaffolds and corticostriatal connectivity in a Shank3 complete knockout model of autism.
Additional
Peripheral Mechanosensory Neuron Dysfunction Underlies Tactile and Behavioral Deficits in Mouse Models of ASDs.
Additional
Novel Shank3 mutant exhibits behaviors with face validity for autism and altered striatal and hippocampal function.
Additional
Comprehensive analysis of two Shank3 and the Cacna1c mouse models of autism spectrum disorder.
Additional
Social deficits in Shank3-deficient mouse models of autism are rescued by histone deacetylase (HDAC) inhibition.
Additional
Dysbiosis of microbiome and probiotic treatment in a genetic model of autism spectrum disorders.
Additional
Heterogeneity of Cell Surface Glutamate and GABA Receptor Expression in Shank and CNTN4 Autism Mouse Models.
Additional
Dietary Zinc Supplementation Prevents Autism Related Behaviors and Striatal Synaptic Dysfunction in Shank3 Exon 13-16 Mutant Mice.
Additional
Mechanisms Underlying Microbial-Mediated Changes in Social Behavior in Mouse Models of Autism Spectrum Disorder.
Additional
An autism-linked missense mutation in SHANK3 reveals the modularity of Shank3 function.
Additional
Striatal Inhibition of MeCP2 or TSC1 Produces Sociability Deficits and Repetitive Behaviors.
Additional
Hypothesis-driven investigations of diverse pharmacological targets in two mouse models of autism.
Additional
Shank3 modulates sleep and expression of circadian transcription factors.

M_SHANK3_1_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Targeted Cre/loxP mediated deletion of exon 4 to exon 9 of Shank3 gene.
Allele Type: Partial knockout
Strain of Origin: Not Specified
Genetic Background: Not Specified
ES Cell Line: Bruce4 C57BL/6
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_SHANK3_1_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Targeted Cre/loxP mediated deletion of exon 4 to exon 9 of Shank3 gene.
Allele Type: Partial knockout
Strain of Origin: Not Specified
Genetic Background: Not Specified
ES Cell Line: Bruce4 C57BL/6
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_SHANK3_4_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Targeted deletion of exon 13 to 16 of Shank3 containing the PDZ domain, the positive selection marker neo cassette is retained.
Allele Type: Partial knockout
Strain of Origin: Not Specified
Genetic Background: C57Bl6*129svJ
ES Cell Line: R1
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_SHANK3_5_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Targeted deletion of exons 4 - 7 containing the ankyrin repeat domains of Shank3 gene, the positive selection marker neo cassette is retained.
Allele Type: Partial knockout
Strain of Origin: Not Specified
Genetic Background: Not Specified
ES Cell Line: R1
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_SHANK3_6_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Targeted deletion of exons 4-9 of Shank3 gene which includes the ankyrin repeat domains.
Allele Type: Partial knockout
Strain of Origin: Not Specified
Genetic Background: Not Specified
ES Cell Line: 129SvEv
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_SHANK3_3_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Deletion of exon 21 of Shank3 resulting in lack of entire C-termain portion of Shank3 (the article reporting this model was retracted, however phenotypic data for the model has been retained following the retraction notification and MGI).
Allele Type: Knockout
Strain of Origin: 129S6/SvEvTac
Genetic Background: Not Specified
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_SHANK3_7_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Targeted deletion of exon 11 within the SH3 domain of Shank3 gene.
Allele Type: Knockout
Strain of Origin: Not specified
Genetic Background: Not Specified
ES Cell Line: Not specified
Mutant ES Cell Line: Not specified
Model Source: Not specified

M_SHANK3_8_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Targeted deletion of exon 21 of the Shank3 gene using cre/loxP and frt flanked neo cassette. After removal of the neo cassette, mice containing the floxed gene were mated to actin-Cre mice for deleting the exon. Wild type Shank3 protein is not detected in these mice. Lower molecular weight isoforms of Shank3 are however detectable.
Allele Type: Knockout
Strain of Origin: 129S6/SvEvTac
Genetic Background: C57BL/6
ES Cell Line:
Mutant ES Cell Line:
Model Source:

M_SHANK3_8_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Targeted deletion of exon 21 (previously described in PMID 24259569); Deletion of exon 21 removes the majority of the Shank3 C-terminus; major isoforms absent but fast migrating truncated fragments present.
Allele Type: Knockout
Strain of Origin: 129S6/SvEvTac
Genetic Background: C57BL/6J
ES Cell Line:
Mutant ES Cell Line:
Model Source: PMID 24259569

M_SHANK3_10_KI_HM_InsG

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Autism-associated guanine nucleotide insertion mutation (Shank3G) present in exon 21 was inserted into the Shank 3 gene, with the construct containing the mutation within exon21 sequence knocked into intron 20 .The additional G results in a frameshift mutation and a premature stop codon downstream of exon 21. Mice containing the Shank3G mutation were crossed for 4 generations with C57BL6J. Het and homozygous mice were generated as littermates.
Allele Type: ASD LOF mutation
Strain of Origin: 129Sv/Evs6
Genetic Background: C57BL/6J*129Sv/Evs6
ES Cell Line: SM-1
Mutant ES Cell Line:
Model Source:

M_SHANK3_10_KI_HT_InsG

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Autism-associated guanine nucleotide insertion mutation (Shank3G) present in exon 21 was inserted into the Shank 3 gene, with the construct containing the mutation within exon21 sequence knocked into intron 20 .The additional G results in a frameshift mutation and a premature stop codon downstream of exon 21. Mice containing the Shank3G mutation were crossed for 4 generations with C57BL6J. Het and homozygous mice were generated as littermates.
Allele Type: ASD LOF mutation
Strain of Origin: 129Sv/Evs6
Genetic Background: C57BL/6J*129Sv/Evs6
ES Cell Line: SM-1
Mutant ES Cell Line:
Model Source:

M_SHANK3_13_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Targeted Cre-LoxP mediated excision of exons 4-9 of Shank3 gene containing the ankyrin repeats. After germline transmission in C57BL6J, knock in mice were mated with mice expressing Flp1 recombinase to excise the Neo cassette used for positive selection. The resulting conditional Shank3 mice were crossed with mice expressing ZP3-Cre to excise exon4-9 in oocytes of female pups, then further crossed with C57BL6J, to homozygosity (Authors do not note that the construct used or the final mice are the same as that reported used in Bozdagi et al Mol Autism (2010) or Yang et al J Neurosci (2012), even if exon 4-9 are targeted in all these studies, therefore they are presumed to be different here).
Allele Type: Knockout
Strain of Origin:
Genetic Background: C57BL/6J
ES Cell Line: 129s6SvEvTac
Mutant ES Cell Line:
Model Source:

M_SHANK3_13_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Targeted Cre-LoxP mediated excision of exons 4-9 of Shank3 gene containing the ankyrin repeats. After germline transmission in C57BL6J, knock in mice were mated with mice expressing Flp1 recombinase to excise the Neo cassette used for positive selection. The resulting conditional Shank3 mice were crossed with mice expressing ZP3-Cre to excise exon4-9 in oocytes of female pups, then further crossed with C57BL6J, to homozygosity (Authors do not note that the construct used or the final mice are the same as that reported used in Bozdagi et al Mol Autism (2010) or Yang et al J Neurosci (2012), even if exon 4-9 are targeted in all these studies, therefore they are presumed to be different here).
Allele Type: Knockout
Strain of Origin:
Genetic Background: C57BL/6J
ES Cell Line: 129s6SvEvTac
Mutant ES Cell Line:
Model Source:

M_SHANK3_15_KI_HM_InsG

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Autism-associated guanine nucleotide insertion mutation (Shank3InsG) was placed at position 3680 in exon 21, this insertion causes a frameshift and a stop codon immediately after the G insertion. The mice were maintained in C57B6/S129Sv background. Mice were bred to homozygosity normally.
Allele Type: ASD LOF mutation
Strain of Origin:
Genetic Background: C57BL/6J*S129Sv
ES Cell Line: R1
Mutant ES Cell Line:
Model Source:

M_SHANK3_15_KI_HT_InsG

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Autism-associated guanine nucleotide insertion mutation (Shank3InsG) was placed at position 3680 in exon 21, this insertion causes a frameshift and a stop codon immediately after the G insertion. The mice were maintained in C57B6/S129Sv background. Mice were bred to homozygosity.
Allele Type: ASD LOF mutation
Strain of Origin:
Genetic Background: C57BL/6J*S129Sv
ES Cell Line: R1
Mutant ES Cell Line:
Model Source:

M_SHANK3_17_KI_HM_R1117X

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Schizophrenia associated non-sense mutation changing arginine to a stop codon (R1117X) was introduced by changing the codon for R 'CGG' to stop codon TGA in position 1117. Mice were maintained in C57Bl6*129Sv background and bred to homozygosity.
Allele Type: NDD LOF mutation
Strain of Origin:
Genetic Background: C57BL/6J*S129Sv
ES Cell Line: R1
Mutant ES Cell Line:
Model Source:

M_SHANK3_17_KI_HT_R1117X

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Schizophrenia associated non-sense mutation changing arginine to a stop codon (R1117X) was introduced by changing the codon for R 'CGG' to stop codon TGA in position 1117. Mice were maintained in C57Bl6*129Sv background.
Allele Type: NDD LOF mutation
Strain of Origin:
Genetic Background: C57BL/6J*S129Sv
ES Cell Line: R1
Mutant ES Cell Line:
Model Source:

M_SHANK3_21_KI_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Targeted knockin inversion of exons 13 to 16, that include the coding region of the PDZ domain, generated using the FLEx genetic switch strategy. The inverted insert is flanked by FRT and loxP sites. The knockin floxed mouse is called a functional knockout by authors.
Allele Type: LOF knockin
Strain of Origin:
Genetic Background: C57BL/6J
ES Cell Line:
Mutant ES Cell Line:
Model Source: Jackson Laboratories

M_SHANK3_22_KI_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Mice with inverted exons 13-16 and the transgene CAGGS-CreER used as controls or parent models. Genotype of these mice is: Shank3fx/fx;CreER+/-.Mice received corn oil treatment (vehicle) at 2-4.5 months.
Allele Type: LOF knockin
Strain of Origin:
Genetic Background: C57BL/6J
ES Cell Line:
Mutant ES Cell Line:
Model Source: Jackson Laboratories

M_SHANK3_19_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Disruption of all murine Shank3 isoforms by cre/loxP mediated excision of exons 4-22 of the Shank3 gene, spanning 58 kb to include the coding sequences for all known Shank3 isoforms. The floxed mice were bred with CMV-cre mice to generate mice with deletions and bred till homozygosity. Authors report loss of all known Shank3 mRNA and protein.
Allele Type: Knockout
Strain of Origin:
Genetic Background: C57BL/6J
ES Cell Line:
Mutant ES Cell Line:
Model Source:

M_SHANK3_19_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Shank3 exon 4-22 floxed mice were bred to CMV-cre mice to generate heterozygous Shank3 knockouts.
Allele Type: Knockout
Strain of Origin:
Genetic Background: C57BL/6J
ES Cell Line:
Mutant ES Cell Line:
Model Source:

M_SHANK3_20_CKO_HM_NAc

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Conditional deletion of exons 4-22 of the Shank3 gene in 10-12 week old female mice by injecting AAV10- Cre virus, bilaterally, in the nucleus accumbens (NAc) to selectively knockdown Shank3 in the Nac
Allele Type: Conditional loss-of-function
Strain of Origin:
Genetic Background: C57BL/6J
ES Cell Line:
Mutant ES Cell Line:
Model Source:

M_SHANK3_4_KO_HT

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Targeted deletion of exon 13 to 16 of Shank3 containing the PDZ domain, the positive selection marker neo cassette is retained.
Allele Type: Partial knockout
Strain of Origin: C57BL/6J
Genetic Background: C57BL/6J*129Sv/Ev
ES Cell Line: R1
Mutant ES Cell Line:
Model Source: PMID 21423165

M_SHANK3_23_KI_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: KI of neo-STOP cassette inserted in intron 12, between exon 12 and exon 13, resulting in loss of higher mol weight Shank3 isoforms, bred to homozygosity. All Shank3 protein expressed in these mutants lacks the PDX domain.
Allele Type: Partial knockout
Strain of Origin: Not Specified
Genetic Background: C57BL/6J
ES Cell Line: 129s6SvEvTac
Mutant ES Cell Line:
Model Source:

M_SHANK3_23_KI_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Neo-STOP cassette was inserted in intron 12, between exon 12 and exon 13, of the Shank3 gene and results in the loss of two higher molecular weight isoforms of Shank3, and results in a protein lacking the PDZ domain.
Allele Type: Partial knockout
Strain of Origin: Not Specified
Genetic Background: C57BL/6J
ES Cell Line: 129s6SvEvTac
Mutant ES Cell Line:
Model Source:

M_SHANK3_4_KO_HM_L-reuteri

Model Type: RESCUE-Transplantation
Model Genotype: Homozygous
Mutation: Adult shank3 knockout mice were treated for three weeks between ages 8-11 weeks, with L. reuteri. Mice were gavaged with 10^9 bacteria of L. reuteri reconstituted in PBS, twice a week for three weeks. Behavioral experimentation was carried out between ages 11-13 weeks, and then mice were immediately sacrificed for downstream molecular and biochemical analysis. L. reuteri used for this study was obtained from ATCC (Lactobacillus reuteri MM4-1A; ATCC-PTA-6475).
Allele Type: Knockout
Strain of Origin: Not Specified
Genetic Background: Not Specified
ES Cell Line:
Mutant ES Cell Line:
Model Source: PMID 21423165

M_Shank3_24_KD

Model Type: Genetic
Model Genotype: Wildtype
Mutation: Seven-week-old wildtype C57BL/6 male mice were injected with Shank3-siRNA (1424750, NM_021423.2), bilaterally in the dorsal striatum, using a stereotaxic apparatus, resulting in a reduction of Shank3 transcript levels to 0.4 fold compared with control siRNA injected mice.
Allele Type: Knockdown
Strain of Origin: C57BL/6
Genetic Background: C57BL/6
ES Cell Line: NA
Mutant ES Cell Line: NA
Model Source: Daehan BioLink (Eumsung, Chungbuk, Republic of Korea)

M_SHANK3_1_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Gene expression1
Decreased
Description: Decreased levels of Shank3 mRNA expression
Exp Paradigm: Shank3 Mrna Expression Levels
 Quantitative PCR (qRT-PCR)
 Unreported
Protein expression level evidence1
Decreased
Description: Decreased levels of Shank3 protein in postsynaptic density extracts
Exp Paradigm: Shank3 Protein Expression Levels
 Western blot
 Unreported
Developmental trajectory1
 No Change
 General observations
 P2-P14
General characteristics1
 No Change
 General observations
 Unreported
Brain morphology1
 No Change
 Histology: Histology
 Unreported
Brain morphology1
 No Change
 Gross necroscopy
 Unreported
Seizures1
 No Change
 General observations
 Unreported
 Not Reported: Circadian sleep/wake cycle, Communications, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Motor phenotype, Neurophysiology, Repetitive behavior, Sensory, Social behavior

M_SHANK3_1_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Structural dendritic plasticity1
Abnormal
Description: Abnormal synaptic potentiation and spine expansion in CA1 neurons
Exp Paradigm: Simultaneous monitoring of spine size and synaptic response in CA1 neurons before and after TBP
 Whole-cell patch clamp
 Unreported
Neuroreceptor activity2
Decreased
Description: Decreased glutamate AMPA receptor component of neuronal sigaling indicated by mean slope of I/O function
Exp Paradigm: Whole cell recordings of hippocampal slices
 Whole-cell patch clamp
 Unreported
Synaptic plasticity: hippocampal LTP1
Decreased
Description: Decreased maintenance of long-term potentiation at Schaffer collateral/CA1 synapses in response to either high-frequency stimulus or TBS
Exp Paradigm: Extracellular fEPSP recordings at Schaffer collateral/CA1 synapses after induction of LTP by tetanic stimulation or TBS
 Field potential recordings
 Unreported
Miniature post synaptic current frequency: excitatory1
Increased
Description: Frequency of mEPSCs is significantly higher in Shank3 hets compared to controls
 Whole-cell patch clamp
 
Synaptic plasticity: hippocampal LTP2
Decreased
Description: Decreased long term potentation induced by high-frequency stimulation
Exp Paradigm: Whole cell recordings of hippocampal slices
 Whole-cell patch clamp
 Unreported
Miniature post synaptic current amplitude: excitatory1
Decreased
Description: Abnormal synaptic transmission demonstrated by decreased amplitude of miniature excitatory postsynaptic currents (mEPSCs) with increased frequency of mEPSCs in hippocampal CA1 pyramidal neurons
Exp Paradigm: Whole cell patch-clamp recordings of spontaneous mEPSCs in the presence of tetrodotoxin in hippocampal CA1 pyramidal neurons
 Whole-cell patch clamp
 3 months
Presynaptic function: paired-pulse facilitation1
Decreased
Description: Decreased paired-pulse ratio in hippocampal CA1 pyramidal neurons
Exp Paradigm: Whole cell patch-clamp recordingsin the presence of tetrodotoxin in hippocampal CA1 pyramidal neurons
 Whole-cell patch clamp
 3 months
Synaptic transmission1
Decreased
Description: Reduced synaptic transmission mediated by AMPA receptor is indicated using antagonist for AMPA/kainate receptors OR NMDA receptor, where the I/O curve is reduced in the Schaffer collateral- CA1 synapses only in the presence of the latter
Exp Paradigm: Extracellular recordings of Schaffer collateral-CA1 synapses in hippocampal slices
 Field potential recordings
 3-4 weeks
Social interaction: opposite sex1
Decreased
Description: Decreased male-female social interaction demonstrated by shorter duration of total social sniffing by male
Exp Paradigm: Direct-contacts between male-female mice
 Reciprocal social interaction test
 2.5-4 months
Ultrasonic vocalization: Interaction induced: opposite sex stimulus1
Decreased
Description: Decreased ultrasonic vocalizations during male-female social interaction
Exp Paradigm: Call latency towards unfamiliar female mouse
 Monitoring ultrasonic vocalizations: reciprocal social interaction test: male-female
 2.5-4 months
Protein expression level evidence1
Decreased
Description: Decreased levels of Shank3 protein in postsynaptic density extracts
Exp Paradigm: Shank3 Protein Expression Levels
 Western blot
 Unreported
Protein expression level evidence1
Decreased
Description: Decreased GluR1 immunoreactive puncta in neurons
Exp Paradigm: Glur1 Protein Expression
 Western blot
 3 months
Gene expression1
Decreased
Description: Decreased levels of Shank3 mRNA expression
Exp Paradigm: Shank3 Mrna Expression Levels
 Quantitative PCR (qRT-PCR)
 Unreported
Developmental trajectory1
 No Change
 General observations
 P2-P14
General characteristics1
 No Change
 General observations
 Unreported
Brain morphology1
 No Change
 Histology: Histology
 Unreported
Brain morphology1
 No Change
 Gross necroscopy
 Unreported
Synaptic plasticity: hippocampal LTD1
 No Change
 Field potential recordings
 Unreported
Seizures1
 No Change
 General observations
 Unreported
Olfaction1
 No Change
 Olfactory habituation-dishabituation test
 2.5-4 months
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / Ultrastructure / Cytoarchitecture, Repetitive behavior, Seizure, Sensory, Social behavior

M_SHANK3_4_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
General locomotor activity: Ambulatory activity7
Decreased
Description: Shank3 null mice show decrease in total distance travelled compared with controls.
 Open field test
 2-3 months, 6-7 months
General locomotor activity4
Decreased
Description: Mutants show decreased activity levels in the home cage compared with controls.
 Home cage behavior
 9-10 weeks
Swimming ability7
Decreased
Description: Shank3 null mice show decrease in swimming speed compared with controls.
 Morris water maze test
 2-3 months
General locomotor activity: Ambulatory activity4
Decreased
Description: Mutants show decrease in total distance travelled compared with controls.
 Home cage behavior
 9-10 weeks
General locomotor activity5
Decreased
Description: Mutants and show decrease in speed of travel on the open field compared with controls, indicating hypoactivity.
 Open field test
 7-10 weeks
Paw preference2
Decreased
Description: In assessments made in Neurocube, Shank3(exon13-16) KO mutants have reductions in variability of paw position, compared to controls and this was one of the important phenotypes that led to differences from controls
 General observations:neurocube
 P30, P60
General locomotor activity: Ambulatory activity5
Decreased
Description: Mutants show decrease in distance travelled on the open field compared with controls, indicating hypoactivity.
 Open field test
 7-10 weeks
General locomotor activity2
Decreased
Description: In the assessments made by Smartcube, the discrimination index for Shank3(exon13-16) KO mutants (differentiating them from controls), was strongly affected by decreased locomotor activity
 General observations:smartcube
 
General locomotor activity: Ambulatory activity2
Decreased
Description: Shank3(exon13-16) KO mutant males exposed to the urine of an estrus female, in the OF arena, mutant males exposed to the urine of an estrus female, in the OF arena, have shorter distance travelled compared to controls
 Open field test in presence of female urine
 Adult
General locomotor activity2
Decreased
Description: Shank3(exon13-16) KO mutants have reduced activity compared to controls in the marble burying test
 Marble-burying test
 Adult
Brain size1
Increased
Description: Increased volumetric enlargement of caudate
Exp Paradigm: Three-Dimensional magnetic resonance imaging of intact brain
 Magnetic resonance imaging (MRI)
 5-6 weeks
Neuronal number: Oxytocin expressing5
Decreased
Description: Mutants show a decrease in oxytocin positive neurons in the PVN of the hypothalamus compared with controls.
 Immunofluorescence staining
 7-10 weeks
Dendritic architecture: spine density1
Increased
Description: Increased dendritic complexity indicative of neuronal hypertrophy due to increased complexity of dendritic arborization, total dendritic length, and surface area
Exp Paradigm: Sholl analysis of golgi stained striatal medium spiny neurons (MSNs)
 Sholl analysis
 5-6 weeks
Post-synaptic density size1
Decreased
Description: Decreased reductikon in mean thickness of Postsynaptic Density (PSD); Decreased PSD length
Exp Paradigm: Electron Microscopy Analysis
 Electron microscopy
 5-6 weeks
Dendritic architecture: spine density1
Decreased
Description: Decreased spine density in medium spiny neurons
Exp Paradigm: Lucifer Yellow cell filling of medium spiny neurons (MSNs)
 Histology: lucifer yellow- medium spiny neurons
 5-6 weeks
Neuroreceptor levels: GABA-R: GABAA3
Decreased
Description: Shank3 mutants show decreased expression of GABA receptors GABRA1, GABRA2, and GABRB1 in the hippocampus, compared to controls. Pearson corelation analysis showed the abundance of L. reuteri, but not L. brevis, or L. ruminis, correlated with expression of each of the three GABA receptor subunits.
 Quantitative PCR (qRT-PCR)
 
Miniature post synaptic current amplitude: excitatory4
Decreased
Description: Mutants show decreased amplitude of evoked AMPAR mediated EPSC amplitudes but no change in NMDAR mediated EPSC amplitudes compared with controls.
Exp Paradigm: Whole-cell patch-clamp recordings were obtained from medial spiny neurons in coronal cortico-striatal brain slices.
 Whole-cell patch clamp
 9-10 weeks
Synaptic transmission1
Decreased
Description: Decreased synaptic transmission indicated by reduced field population spikes
Exp Paradigm: Extracellular recordings of cortico-striatal synaptic circuitry in acute brain slices
 Field potential recordings
 6-7 weeks
Decay kinetics of miniature post synaptic currents4
Decreased
Description: Mutants show slowed decay kinetics compared with controls, measured by an increased in the weighted decay tau.
Exp Paradigm: Whole-cell patch-clamp recordings were obtained from medial spiny neurons in coronal cortico-striatal brain slices.
 Whole-cell patch clamp
 9-10 weeks
Synaptic plasticity: ventral tegmental area LTP5
Decreased
Description: Mutants show decrease in AMPAR/NMDAR ratio in response to social interaction, in the VTA compared with controls, indicating a decrease in LTP in the VTA.
Exp Paradigm: Direct social interaction-evoked long-term potentiation (LTP) in VTA DA neurons was recorded.
 Whole-cell patch clamp
 7-10 weeks
Miniature post synaptic current frequency: excitatory4
Increased
Description: Mutants show increased frequency of evoked EPSC frequencies compared with controls.
Exp Paradigm: Whole-cell patch-clamp recordings were obtained from medial spiny neurons in coronal cortico-striatal brain slices.
 Whole-cell patch clamp
 9-10 weeks
Synaptic transmission: excitatory1
Abnormal
Description: Abnormal postsynaptic function demonstrated by decreased frequency and amplitude of AMPAR-mEPSCs of MSNs
Exp Paradigm: Whole-cell voltage clamp recordings of AMPAR-mESPCS in dorsolateral striatal medium spiny neurons (MSNs)
 Whole-cell patch clamp
 6-7 weeks
Self grooming: perseveration2
Increased
Description: In the assessments made by Smartcube, the discrimination index for Shank3(exon13-16) KO mutants (differentiating them from controls), was strongly affected by increase in grooming
 Grooming behavior assessments
 
Self grooming: perseveration2
Increased
Description: Shank3(exon13-16) KO mutants show increased balding and some skin lesions compared to controls
 Grooming behavior assessments
 4.5 months, 6 months
Repetitive digging2
Decreased
Description: Shank3(exon13-16) KO mutants bury less number of marbles than controls in the marble-burying test
 Marble-burying test
 Adult
Self grooming: perseveration7
Increased
Description: Shank3 null mice show increased self grooming compared with controls in the standard empty cage in two separate cohorts.
 Novel cage test
 2-3 months, 6-7 months
Repetitive digging3
Increased
Description: Shank3 mutants buried more marbles than controls.
 Marble-burying test
 
Self grooming: perseveration4
Increased
Description: Mutants show increase in self grooming compared with controls.
 Grooming behavior assessments
 9-10 weeks
Startle response: acoustic stimulus2
Decreased
Description: Shank3(exon13-16) KO mutants have significantly reduced acoustic startle reflex
 Acoustic startle reflex test
 Adult
Sensorimotor gating2
Decreased
Description: Shank3(exon13-16) KO mutants have impaired sensorimotor gating compared to controls
 Prepulse inhibition
 Adult
Social interaction1
Decreased
Description: Decreased reciprocal interaction, frequency of nose-to-nose interaction and anogenital sniffing
 Reciprocal social interaction test
 5-6 weeks
Social approach1
Decreased
Description: Decreased social interaction behavior demonstrated by clear preference for interacting with empty cage
Exp Paradigm: Modified three-chambered social arena task
 Three-chamber social approach test
 5-6 weeks
Social interaction: opposite sex7
Decreased
Description: Male Shank3 null mice show decreased interaction with an estrus B6 female compared with controls as measured by a decrease in nose-to-nose interaction bouts. Male Shank3 null mice show no change in nose to nose interaction duration, nose to anogenital interaction bouts or duration, following bouts or duration or approaches with an estrus B6 female compared with controls.
 Reciprocal social interaction test
 6-16 weeks
Social approach4
Decreased
Description: Mutants spent less time sniffing an unfamiliar mouse compared with controls.
 Three-chamber social approach test
 9-10 weeks
Self grooming: social context7
Increased
Description: Shank3 null mice show increased self grooming compared with controls in the presence of an estrus female.
 Grooming behavior assessments
 2-3 months
Social interaction2
Increased
Description: Shank3(exon13-16) KO mutants spend increased time interacting with stimulus mouse compared to controls
 Reciprocal social interaction test
 Adult
Social approach5
Decreased
Description: Mutants show reduced preference for an unfamiliar mouse in comparison to an empty cup compared with controls.
 Three-chamber social approach test
 7-10 weeks
Social memory4
Decreased
Description: Mutants show no preference for a novel mouse compared with controls.
 Three-chamber social approach test
 9-10 weeks
Social interaction5
Decreased
Description: Mutants spent less time interacting socially compared with controls.
 Reciprocal social interaction test
 7-10 weeks
Social approach3
Decreased
Description: Male shank3 mutants spent less time investigating the compartment with the unfamiliar mouse and more time in the empty chamber compared to controls. Female shank3 mutants show no preference between the empty and occupied compartments, compared to controls.
 Three-chamber social approach test
 
Social memory1
Abnormal
Description: Abnormal social novelty demonstrated by decreased time interacting with novel mouse
Exp Paradigm: Modified three-chambered social arena task with introduction of a novel social partner
 Three-chamber social approach test
 5-6 weeks
Ultrasonic vocalization: Interaction induced: opposite sex stimulus7
Decreased
Description: Male Shank3 null mice show decrease in the number of ultrasonic vocalizations emitted compared with controls (4J,K). Male Shank3 null mice show no change in the number of ultrasonic vocalizations emitted compared with controls (S13H).
 Monitoring ultrasonic vocalizations
 6-16 weeks
Ultrasonic vocalization: Interaction induced: opposite sex stimulus2
Decreased
Description: Shank3(exon13-16) KO mutant males exposed to the urine of an estrus female, in the OF arena, emitted fewer vocalizations compared to controls
 Open field test in presence of female urine
 Adult
Size/growth2
Increased
Description: At P60 and later Shank3 (exon 13-16) mutants had increased body weight compared to controls
 Body weight measurement
 P60
Developmental trajectory1
Abnormal
Description: Abnormal developmental trajectory indicated by development of pronounced skin lesions with varying degrees of penetrance
 General observations
 4-5 months
Anxiety3
Increased
Description: Male shank3 mutants spent less time in the center of the open field compared to controls.
 Open field test
 
Anxiety2
Increased
Description: Shank3(exon13-16) KO mutant males exposed to the urine of estrus female display increased anxiety as they spend less time in the center of the open field arena
 Open field test in presence of female urine
 Adult
Anxiety1
Increased
Description: Increased anxiety demonstrated by: reduced rearing activity which is a form of vertical exploration, less time exploring open arms of maze, increased latency to cross brightly lit area
Exp Paradigm: Open field test measurement of rearing; Elevated Zero Maze; Light-Dark emergence test-Open field test
 Open field test
 5-6 weeks
Anxiety4
Increased
Description: Mutants spent less time in the light chamber, show increased latency to enter the light chamber, and show decrease in the number of alterations between the light and dark chambers, compared with controls.
 Light-dark exploration test: Light-dark exploration test
 9-10 weeks
Anxiety1
Increased
Description: Increased anxiety demonstrated by: reduced rearing activity which is a form of vertical exploration, less time exploring open arms of maze, increased latency to cross brightly lit area
Exp Paradigm: Open field test measurement of rearing; Elevated Zero Maze; Light-Dark emergence test- Light-dark exploration test
 Light-dark exploration test: Light-dark exploration test
 5-6 weeks
Anxiety3
Increased
Description: Male shank3 mutants spent less time in the open arms of the elevated plus maze compared to controls.
 Elevated plus maze test
 
Anxiety1
Increased
Description: Increased anxiety demonstrated by: reduced rearing activity which is a form of vertical exploration, less time exploring open arms of maze, increased latency to cross brightly lit area
Exp Paradigm: Open field test measurement of rearing; Elevated Zero Maze; Light-Dark emergence test- Elevated zero maze test
 Elevated zero maze test
 5-6 weeks
Exploratory activity2
Decreased
Description: Shank3(exon13-16) KO mutants' latency of approach stimulus, rearing etc was one of the top features contributing to the difference between mutant and wild type mice in smartcube analysis
 General observations:smartcube
 
Cytokine levels: pro-inflammatory3
Decreased
Description: Shank3 mutants show decreases in plasma IL-1b, IL-17a and TNF-a in females compared to controls.
 ELISA
 
Cytokine levels: pro-inflammatory3
Increased
Description: Shank3 mutants show increases in plasma IFN-gamma, IL-17a and TNF-alpha in males, compared to controls.
 ELISA
 
Cytokine levels: pro-inflammatory3
Increased
Description: Shank3 mutants show increases in plasma IFN-gamma, IL-6 in females compared to controls.
 ELISA
 
Cytokine levels: anti-inflammatory3
Increased
Description: Shank3 mutants show increases in plasma IL-10 in both sexes, compared to controls.
 ELISA
 
Cytokine levels: pro-inflammatory3
Decreased
Description: Shank3 mutants show decreases in plasma IL-6 and IL-1b in males compared to controls.
 ELISA
 
Spatial learning7
Decreased
Description: Shank3 null mice show greater latency to reach the hidden platform over multiple trials compared with controls.
 Morris water maze test
 2-3 months
Spatial reference memory7
Decreased
Description: Shank3 null mice spent more time in the target quadrant and crossed the platform zone more number of times, 5 hours but not 24 hours after the last training session, during the probe trial session.
 Morris water maze test
 2-3 months
Protein expression level evidence6
Decreased
Description: Mutants show decrease in ABI1 abundance in the striatal post synaptic density fraction compared with controls.
 Western blot
 Adult
Protein expression level evidence1
Decreased
Description: Decreased levels of SAPAP3, Homer-1b/c, PSD-93, GluR2, NR2A and NR2B in PSD's derived from striatum
Exp Paradigm: Psd Protein Network
 Western blot
 5-6 weeks
Gene expression3
Decreased
Description: Shank3 mutants show decreased levels of oxytocin gene expression in the hypothalamus compared to controls.
 Quantitative PCR (qRT-PCR): oxytocin
 
Ultrasonic vocalization: Isolation induced2
 No Change
 Monitoring ultrasonic vocalizations
 P4,P7, P15
Developmental trajectory2
 No Change
 Developmental milestone measurements
 P4, P7, P13
Size/growth1
 No Change
 General observations
 Unreported
Size/growth2
 No Change
 Body weight measurement
 P4-P30
Anxiety5
 No Change
 Open field test
 7-10 weeks
Exploratory activity2
 No Change
 Three-chamber social approach test
 ~P45
Cognitive flexibility2
 No Change
 Procedural water T-maze
 Adult
Object recognition memory1
 No Change
 Grooming behavior assessments
 3-6 months
Procedural learning2
 No Change
 Procedural water T-maze
 Adult
Spatial reference memory1
 No Change
 Morris water maze test
 5-6 weeks
Swim distance7
 No Change
 Morris water maze test
 2-3 months
Gene expression5
 No Change
 Quantitative PCR (qRT-PCR)
 7-10 weeks
Protein expression level evidence6
 No Change
 Western blot
 Adult
Protein expression: In situ protein expression4
 No Change
 Immunohistochemistry
 9-10 weeks
Gait2
 No Change
 General observations:neurocube
 P30, P60
General locomotor activity1
 No Change
 Open field test
 5-6 weeks
Motor coordination and balance1
 No Change
 Accelerating rotarod test
 5-6 weeks
Negative Geotaxis2
 No Change
 Negative geotaxis test
 P4, P7, P15
Righting response2
 No Change
 Righting reflex test
 P4, P7, P15
Brain anatomy1
 No Change
 Histology: macroscopic analysis
 5-6 weeks
Brain cytoarchitecture1
 No Change
 Histology: lucifer yellow- medium spiny neurons
 5-6 weeks
Brain size1
 No Change
 Magnetic resonance imaging (MRI)
 5-6 weeks
Neuronal number in the brain5
 No Change
 Immunofluorescence staining
 7-10 weeks
Presynaptic function: paired-pulse facilitation1
 No Change
 Field potential recordings
 6-7 weeks
Synaptic plasticity: post-tetanic potentiation (PTP)4
 No Change
 Whole-cell patch clamp
 9-10 weeks
Synaptic transmission1
 No Change
 Field potential recordings
 6-7 weeks
Synaptic transmission: excitatory1
 No Change
 Whole-cell patch clamp
 6-7 weeks
Digestive system function: intestinal barrier: intestinal permeability5
 No Change
 Intestinal permeability test: FITC-dextran injection
 7-10 weeks
Hypothermia2
 No Change
 Body temperature measurement
 P4, P15
Intestinal microbiota composition: overall microbiota composition5
 No Change
 16S rRNA gene sequence analysis for identification of bacteria
 7-10 weeks
Seizures1
 No Change
 General observations
 5-6 weeks
Olfaction5
 No Change
 Buried food test
 7-10 weeks
Olfaction2
 No Change
 General observations
 P4, P7, P15
Social approach2
 No Change
 Three-chamber social approach test
 ~P45
Social memory5
 No Change
 Three-chamber social approach test
 7-10 weeks
Social memory2
 No Change
 Three-chamber social approach test
 ~P45
Social scent marking or recognition2
 No Change
 Open field test in presence of female urine
 Adult
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / Ultrastructure / Cytoarchitecture, Neurophysiology, Repetitive behavior, Seizure, Sensory, Social behavior

M_SHANK3_5_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Social memory1
Abnormal
Description: Abnormal social novelty demonstrated by decreased time interacting with novel mouse
Exp Paradigm: Modified three-chambered social arena task with introduction of a novel social partner
 Three-chamber social approach test
 Unreported
Developmental trajectory1
 No Change
 General observations
 3-6 months
Size/growth1
 No Change
 General observations
 Unreported
Anxiety1
 No Change
 Elevated zero maze test
 Unreported
Anxiety1
 No Change
 Light-dark exploration test: Light-dark exploration test
 Unreported
Anxiety1
 No Change
 Open field test
 Unreported
Social approach1
 No Change
 Three-chamber social approach test
 Unreported
 Not Reported: Circadian sleep/wake cycle, Communications, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / Ultrastructure / Cytoarchitecture, Neurophysiology, Repetitive behavior, Seizure, Sensory

M_SHANK3_6_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Grip strength1
Decreased
Description: Decreased motor strength demonstrated by delayed climbing and abnormal vertical placement
Exp Paradigm: Vertical pole test
 Vertical pole test
 Unreported
Paw preference2
Decreased
Description: In assessments made in Neurocube, Shank3(exon4-9) KO mutants have differences from controls in variability of paw position at P60
Exp Paradigm: Neurocube
 Paw preference test
  P60
General locomotor activity: Ambulatory activity2
Decreased
Description: Shank3 (exon 4-9) KO mutant males exposed to the urine of an estrus female, in the OF arena, mutant males exposed to the urine of an estrus female, in the OF arena, have shorter distance travelled compared to controls
 Open field test in presence of female urine
 Adult
Motor coordination and balance1
Decreased
Description: Decreased motor learning demonstrating by No Change in latency to fall
Exp Paradigm: Male mice: Accelerating rotarod test
 Accelerating rotarod test
 Unreported
General locomotor activity1
Decreased
Description: Decreased locomotion; No Change in time spent moving, rearing, stereotypical activities
Exp Paradigm: Open field test
 Open field test
 Unreported
Motor coordination and balance1
Decreased
Description: Decreased motor coordination demonstrated by increased foot baults, slower movement pace
Exp Paradigm: Foot-misplacement test
 Footslip test
 Unreported
Head bobbing1
Increased
Description: Increased head pokes
Exp Paradigm: Novel environment hole-board test; Novel object test
 Hole-board test
 Unreported
Social interaction1
Decreased
Description: Decreased social interactions with tendency to participate in non-social self focused behaviors
Exp Paradigm: Dyadic test for social behavior
 Reciprocal social interaction test
 3-6 months
Social approach3
Decreased
Description: Shank3 mutants with ablated exons 4-9 spend less time exploring a social stimulus compared to controls.
 Three-chamber social approach test
 5-8 weeks
Ultrasonic vocalization1
Abnormal
Description: Abnormal ultrasonic vocalization: Decreased number of calls, decreased call pattern complexity, increased high frequency calls for shorter durations
Exp Paradigm: Female mice:
 Monitoring ultrasonic vocalizations
 3-4 months
Ultrasonic vocalization: Interaction induced: opposite sex stimulus2
Decreased
Description: Shank3 (exon 4-9) KO mutant males exposed to the urine of an estrus female, in the OF arena, emitted fewer vocalizations compared to controls
 Open field test in presence of female urine
 Adult
Ultrasonic vocalization1
Abnormal
Description: Abnormal ultrasonic vocalization: Increased number of calls, decreased call pattern complexity, No Change in call frequency across duration
Exp Paradigm: Male mice:
 Monitoring ultrasonic vocalizations
 3-4 months
Size/growth1
Increased
Description: Increased body weight
Exp Paradigm: General observations
 General observations
 8-12 months
Exploratory activity2
Decreased
Description: Shank3 (exon 4-9) KO mutants displayed less exploration of the two chambers in the three chamber social approach test during the habituation phase
 Three-chamber social approach test
 ~P45
Anxiety2
Increased
Description: Shank3 (exon 4-9) KO mutant males exposed to the urine of estrus female display increased anxiety as they spend less time in the center of the open field arena
 Open field test in presence of female urine
 Adult
Gene expression3
Increased
Description: Shank3 mutants with ablated exons 4-9 show increase in Hdac2 transcript, compared to controls.
 Western blot: nuclear fraction
 5-6 weeks
Protein localization: nucleus3
Increased
Description: In the PFC of shank3 mutant mice with ablation of exons 4-9, the level of β-catenin in the nucleus was increased compared to controls.
 Western blot: beta-catenin
 5-6 weeks
Gene expression1
Abnormal
Description: Abnormal Shank3 species indicated by two smaller products (330 bp and 260 bp)
Exp Paradigm: Shank3 Mrna Species
 Western blot
 Unreported
Protein expression level evidence3
Increased
Description: Shank3 mutants with ablated exons 4-9 show increase in Hdac2 protein, compared to controls.
 Western blot: nuclear fraction
 5-6 weeks
Protein expression level evidence1
Decreased
Description: Decreased expression of full-length Shank3 protein
Exp Paradigm: Shank3 Protein Expression Levels
 Western blot
 Unreported
Protein localization: synapse3
Decreased
Description: In the PFC of shank3 mutant mice with ablation of exons 4-9, β-catenin at the synaptic membrane fraction was significantly reduced, compared to controls.
 Western blot: beta-catenin
 5-6 weeks
Ultrasonic vocalization: Isolation induced2
 No Change
 Monitoring ultrasonic vocalizations
 P4,P7, P15
Developmental trajectory2
 No Change
 Developmental milestone measurements
 P4, P7, P13
General characteristics1
 No Change
 General observations
 Unreported
Size/growth1
 No Change
 General observations
 3-4 months
Size/growth2
 No Change
 Body weight measurement
 P4-P90
Anxiety1
 No Change
 Elevated zero maze test
 Unreported
Anxiety1
 No Change
 Light-dark exploration test: Light-dark exploration test
 Unreported
Response to novelty1
 No Change
 Zero maze test
 Unreported
Response to novelty1
 No Change
 Open field test
 Unreported
Cognitive flexibility2
 No Change
 Procedural water T-maze
 Adult
Procedural learning2
 No Change
 Procedural water T-maze
 Adult
Gait2
 No Change
 General observations:neurocube
 P30, P60
General locomotor activity2
 No Change
 Marble-burying test
 Adult
Motor coordination and balance1
 No Change
 Accelerating rotarod test
 Unreported
Negative Geotaxis2
 No Change
 Negative geotaxis test
 P4, P7, P15
Paw preference2
 No Change
 General observations:neurocube
 P30
Righting response2
 No Change
 Righting reflex test
 P4, P7, P15
Hypothermia2
 No Change
 Body temperature measurement
 P4, P7, P15
Repetitive digging2
 No Change
 Marble-burying test
 Adult
Self grooming: perseveration2
 No Change
 Grooming behavior assessments
 4.5 months, 6 months
Olfaction1
 No Change
 Urine preference test
 Unreported
Olfaction2
 No Change
 General observations
 P4, P7, P15
Sensorimotor gating2
 No Change
 Prepulse inhibition
 Adult
Startle response: acoustic stimulus2
 No Change
 Acoustic startle reflex test
 Adult
Social approach1
 No Change
 Three-chamber social approach test: sociability
 3-6 months
Social approach2
 No Change
 Three-chamber social approach test
 ~P45
Social interaction2
 No Change
 Reciprocal social interaction test
 ~P45
Social memory2
 No Change
 Three-chamber social approach test
 ~P45
Social scent marking or recognition2
 No Change
 Open field test in presence of female urine
 Adult
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / Ultrastructure / Cytoarchitecture, Neurophysiology, Repetitive behavior, Seizure, Sensory

M_SHANK3_3_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Neuroreceptor levels: glutamate receptors: NMDA receptors1
Decreased
Description: Decreased levels of NMDAR subunit NR1 levels in cortex
Exp Paradigm: Immunoblot analysis from cortical lysates
 Western blot
 2 months
Synaptic transmission1
Decreased
Description: Decreased ratio of NMDA/AMPA-dependent evoked responses in cortex
Exp Paradigm: Whole cell recordings
 Whole-cell patch clamp
 Unreported
Protein expression level evidence1
Decreased
Description: Decreased Shank3 protein levels in cortical lysates
Exp Paradigm: Shank3 Protein Expression Levels
 Western blot
 8 weeks
Signaling2
Decreased
Description: Actin signaling is significantly downregulated in the prefrontal cortex of Shank3 het mice (ankyrin repeats deleted) determined by significant changes in expression profile from the cortical protein synaptic density (PSD) fractions , in two dimensional fluorescence difference gel electrophoresis. Significant reduction in p-cofilin (inactive cofilin) and LIMK1 were observed.
Exp Paradigm: Males only
 Two-dimensional flourescence difference gel electrophoresis (2-DIGE): actin levels in protein synaptic density (PSD) fraction
 6-8 weeks
Protein ubiquitination1
Increased
Description: Increased polyubiquitination of Shank3 in cortex
Exp Paradigm: In Vivo Polyubiquitination
 Western blot
 Unreported
General characteristics1
 No Change
 General observations
 Unreported
Size/growth1
 No Change
 General observations
 Unreported
Neuroreceptor levels: glutamate receptors: NMDA receptors1
 No Change
 Western blot
 2 months
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Motor phenotype, Neuroanatomy / Ultrastructure / Cytoarchitecture, Neurophysiology, Repetitive behavior, Seizure, Sensory, Social behavior

M_SHANK3_7_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Neuroreceptor levels: glutamate receptors: NMDA receptors2
Decreased
Description: Mutants show reduced expression of cell surface GluN1 compared to controls, in the striatum and thalamus. Mutants show no change in the total expression of analyzed receptors.
 Western blot
 3-6 months
Neuroreceptor levels: glutamate receptors: AMPA receptors2
Decreased
Description: Mutants show reduced expression of cell surface GluA2 compared to controls, in the striatum and thalamus. Mutants show reduced expression of cell surface GluA1 compared to controls, in the hippocampus and striatum. Mutants show no change in the total expr
 Western blot
 3-6 months
Protein expression level evidence1
Increased
Description: Increased Shank2 protein levels in whole brain PSD's
Exp Paradigm: Shank2 Protein Levels
 Western blot
 Unreported
Protein expression level evidence1
Increased
Description: Increased synaptic content of ionotropic glutamate receptor
Exp Paradigm: Ionotropic Glutamate Receptor Content
 Western blot
 Unreported
Gene expression1
 No Change
 Semi-quantitative PCR (qRT-PCR)
 Unreported
Dendritic architecture: spine density1
 No Change
 Golgi-Cox staining
 Unreported
Neuroreceptor levels: GABA-R: GABAA2
 No Change
 Western blot
 3-6 months
Neuroreceptor levels: glutamate receptors: AMPA receptors2
 No Change
 Western blot
 3-6 months
Neuroreceptor levels: glutamate receptors: NMDA receptors2
 No Change
 Western blot
 3-6 months
Synaptic morphology1
 No Change
 Electron microscopy
 Unreported
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neurophysiology, Repetitive behavior, Seizure, Sensory, Social behavior

M_SHANK3_8_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Circadian rhythms: timing/phases of locomotor activity4
Decreased
Description: Mutants show decreased wheel turning activity in constant darkness compared with controls measured by the number of wheel revolutions, indicating abnormality in circadian rhythms. Mutants show no change in length of the active phase or the time between the start of one active phase to the start of the subsequent active phase in constant darkness compared with controls. Mutants show increase in wheel turning activity under 5 weeks of continuous light-dark cycles, compared with controls.
Exp Paradigm: Wheel-running was measured for 2 weeks under might-dark followed by 3 weeks in constant darkness; or 5 weeks of continuous light-dark cycles.
 Wheel running monitoring
 9, 11 weeks
Sleep pattern: Total nighttime sleep4
Decreased
Description: Mutants sleep less and spend more time awake during the dark period compared with controls. Mutants also show decrease in total time spent in NREM and REM sleep during the light and dark hours compared with controls.
 Electroencephalogram/electromyogram (EEG/EMG)
 12 weeks
Sleep pattern: Number of sleep bouts4
Decreased
Description: Mutants show decrease in bout number of REM sleep between 19 and 24 hours of the dark cycle compared with controls but no change in the bout number for NREM sleep.
 Electroencephalogram/electromyogram (EEG/EMG)
 12 weeks
Sleep pattern: Sleep recovery4
Decreased
Description: Mutants spent more time in wakefulness and less time in NREM and REM sleep near the end of the dark period after sleep deprivation compared with controls. Mutants show no change in reduced wakefulness, increased time spent in NREM and REM sleep, and increase in sleep consolidation during the total recovery phase following sleep deprivation compared with controls. Mutants show no change in NREM EEG delta power compared with controls, indicating that mutant mice accumulate similar sleep pressure post sleep deprivation. Mutants show increase of NREM EEG spectral power compared with controls in the first 2hours post sleep deprivation in the higher frequencies (3.9-19.5 Hz) compared with controls, indicating abnormal homeostatic response to sleep deprivation.
Exp Paradigm: Mutant and WT mice were sleep deprived for 5 hours.
 Electroencephalogram/electromyogram (EEG/EMG)
 9, 11 weeks
Rapid Eye Movement Sleep (REMS)4
Decreased
Description: Mutants spend less time in REM sleep, particularly at ZT hour 19 compared with controls.
 Electroencephalogram/electromyogram (EEG/EMG)
 12 weeks
Sleep pattern: Sleep latency4
Increased
Description: Mutants took longer to enter NREM sleep after sleep deprivation compared with controls.
Exp Paradigm: Mutant and WT mice were sleep deprived for 5 hours.
 Electroencephalogram/electromyogram (EEG/EMG)
 9, 11 weeks
Non Rapid Eye Movement Sleep (NREMS)4
Decreased
Description: Mutants spend less time in NREM sleep, particularly at ZT hour 19, compared with controls.
 Electroencephalogram/electromyogram (EEG/EMG)
 12 weeks
Sleep pattern: Sleep bout length1
Decreased
Description: Mutants show decrease in NREM and REM bout duration at the end of the dark cycle compared with controls at 19 to 24 hours.
 Electroencephalogram/electromyogram (EEG/EMG)
 12 weeks
Motor coordination and balance1
Decreased
Description: Shank3 mutant mice have reduced time to fall of the rotarod than wild type control animals.
Exp Paradigm: Males and females
 Accelerating rotarod test
 2-6 months
Synaptic neuroreceptors1
Increased
Description: Shank3 mutant mice have increased levels of mGluR5 in the synaptosomal and postsynaptic density fraction in the hippcampal lysates.
 Western blot: hippocampal lysate
 5-6 months
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission1
Decreased
Description: Synaptic transmission dependent on the NMDAR/AMPAR ratio is reduced in Shank3 mutants. It is determined using amplitude/frequency of miniature EPScs that NMDAR mediated currents are reduced
Exp Paradigm: Males only
 Whole-cell patch clamp
 3-4 months
Miniature post synaptic current frequency: excitatory1
Decreased
Description: The frequencey of mEPSCs in hippocampal synapses in the Shank3 mutant mice was signficantly reduced, indicatinga possible decrease in the number of CA3-CA1 synapses
Exp Paradigm: Males only
 Whole-cell patch clamp
 P13-17
Synaptic transmission1
Decreased
Description: The input/output relationship of stimulus intensity to slope of fEPSP is decreased in Shank3 mutant mice, which may indicate a reduction in the number of functional CA3-CA1 synapses
Exp Paradigm: Males only
 Field potential recordings
 P13-17
Event related oscillations (EROs) in electroencephalography (EEG)4
Abnormal
Description: Mutants show decrease in delta frequencies (0.5-4 Hz) and increase in alpha frequencies (10-15 Hz) during NREM sleep compared with controls, resulting in significant change in spectral frequencies at 95% confidence interval.
Exp Paradigm: NREM delta power is a measure of synchrony of the neural network and can be a measure of sleep intensity or depth.
 Electroencephalogram (EEG)
 9, 11 weeks
Synaptic plasticity: hippocampal LTP1
Decreased
Description: LTP was significantly impaired in the CA1 region of Shank3 mutants compared to wild type controls
Exp Paradigm: Males only
 Field potential recordings
 3-4 months
Repetitive digging1
Decreased
Description: Shank3 mutant mice have a significantly reduced number of marbles buried in the marble burying test, compared to wild type controls
Exp Paradigm: Males and females
 Marble-burying test
 2-6 months
Self grooming: perseveration1
Increased
Description: Older Shank3 mutant mice have increased levels of grooming in the number of bouts and time spent, in a novel environment (new cage)
Exp Paradigm: Males and females
 Grooming behavior assessments
 10-13 months
Self grooming: perseveration3
Increased
Description: Excessive self-grooming in Shank3 KO but not Shank3 HT mice
Exp Paradigm: To monitor spontaneous self-grooming, mice were placed in a clean cage (identical to the home cage), with minimal bedding to discourage digging, which was then placed in a sound-proof box for video monitoring; Animals were habituated in the new cage for 10 minutes before self-grooming was monitored during another 10 minutes; Cumulative grooming time was reported for this second 10 minute period;
 Grooming behavior assessments
 Adult
Pain or nociception1
Increased
Description: Shank3 mutant mice show increased pain perception as the latency to lick their paw after a foot shock has been delivered is lower in these mice compared to wild type controls
Exp Paradigm: Males and females
 Hot plate test
 2-6 months
Social memory1
Decreased
Description: Shank3 mutant mice have reduced memory of a familiar stimulus mouse as they spend a similar amount of time interacting with the familiar and novel stimulus mice in the three chamber social approach test
Exp Paradigm: Males and females
 Three-chamber social approach test: interaction with juvenile target mice
 2-6 months
Inanimate object preference1
Decreased
Description: Shank3 mutant mice have a high propensity to avoid all new objects.
Exp Paradigm: Males and females
 Three-chamber social approach test
 2-6 months
Social approach3
Decreased
Description: Social investigation reduced in Shank3 KO but not Shank3 HT mice
Exp Paradigm: Mice were tested for social motivation and social novelty in a three-chamber arena over three phases; In Phase 1, identical inanimate objects (inverted ceramic cups with blue stripe) were placed in both side chambers; In phase 2, social interaction with a novel intruder is measured relative to a previously encountered object from phase 1; Phase 3 tests for social novelty with a second intruder;
 Three-chamber social approach test
 Adult
Social approach2
Decreased
Description: Shank3 mutant mice have reduced preference for the stimulus mouse compared to wild type controls.
Exp Paradigm: Males only
 Three-chamber social approach test
 6-8 weeks
Nest building behavior1
Decreased
Description: Shank3 mutant mice show significantly reduced nest building behavior, showing no change in their nestlets, whereas wild type controls readily made nests from the material.
Exp Paradigm: Males and females
 Nest building assay
 2-6 months
Response to novelty1
Decreased
Description: Shank3 mutants show reduced response to novelty, unlike wild type controls, as they have reduced locomotor activity in the novel environment of the open field test
Exp Paradigm: Males and females
 Open field test
 2-6 months
Exploratory activity3
Decreased
Description: Increased avoidance behavior or decreased exploratory behavior present in both Shank3 KO and HT mice
Exp Paradigm: Decreased marble-burying in both Shank3 KO and HT mice
 Marble-burying test
 Adult
Anxiety1
Increased
Description: Shank3 mutant mice show increased anxiety-like behavior in the light/dark box test as they have a very high latency to explore the dark box and spend very little tim in the dark box. Authors have noted that this may be attributable to increase in avoidance behavior, rather in increase in anxiety.
Exp Paradigm: Males and females
 Light-dark exploration test: Light-dark exploration test
 2-6 months
Spatial reference memory1
Decreased
Description: Shank3 mutant mice show significantly reduced memory of the position of the platform, despite spending increased amount of time in the correct quadrant compared to other quadrants. Number of crossings at the are significantly lower in shank3 mutants compared to wild type controls in both the probe trial and the probe trial of the reversal phase of Morris water maze
Exp Paradigm: Males and females
 Morris water maze test: probe trial and reversal phase probe trial
 2-6 months
Spatial learning1
Decreased
Description: Shank3 mutant mice show reduced spatial learning measured by latency to reach the hidden platform, in the Morris water maze test. They take longer times to reach the platform compared to wild type controls
Exp Paradigm: Males and females
 Morris water maze test: latency and distance travelled in the hidden platform trials
 2-6 months
Gene expression4
Increased
Description: Mutants show upregulation of genes involved in cholesterol metabolism (Hmgcr, Insig1) and transcription (Jun, Fosl2, Nfil3, Stat4) under normal home cage conditions and upregulation of genes involved in potassium ion transport (Kcnv1, Kcnk1, Kcnk2), dephosphorylation (Dusp10, Dusp3, and Ptprj) and neuron projection development (Cntn1, Ntrk2, Reln, and Sema3a) under conditions of sleep deprivation, indicating sleep deprivation exacerbates baseline differences in gene expression.
Exp Paradigm: Mice were subjected to 5 hours of sleep deprivation. Gene expression was quantified in the prefrontal cortex.
 RNA sequencing
 8-10 weeks
Gene expression4
Decreased
Description: Mutants show downregulation of genes involved in MAPK signaling (Mapk3, Elk1), Circadian rhythms (Per3, Tef, Hlf) and transcription (Tef, Hlf) under normal homecage conditions and downregulation of genes involved in GnRH signaling (Mapk1, Elk1, Mapk11), circadian rhythms (Per3, Nr1d1, Tef, Hlf, Prkab2, Bhlhe41) and sodium ion transport (Slc6a15, Slc22a4 and Slc24a4) under sleep deprived condition, indicating sleep deprivation exacerbates baseline differences in gene expression.
Exp Paradigm: Mice were subjected to 5 hours of sleep deprivation. Gene expression was quantified in the prefrontal cortex.
 RNA sequencing
 8-10 weeks
Targeted expression2
Decreased
Description: Shank3 full length isoforms show a reduction of 85% in the synaptosomal and total fractions of frontal cortical lysates from homozygous knockout mice, compared to wild type
 Western blot: frontal cortex lysate
 
Protein expression level evidence3
Increased
Description: Inreased CLK2 protein in knockout mice neurons
Exp Paradigm: Primary cortical neurons were stimulated with BDNF (to elicit synaptic-plasticity dependent changes) on the 16th day in vitro and harvested in RIPA buffer for SDS-PAGE and Western blotting;
 Western blot
 E16
Sleep pattern: Total daytime sleep4
 No Change
 Electroencephalogram/electromyogram (EEG/EMG)
 12 weeks
Ultrasonic vocalization: Interaction induced: opposite sex stimulus1
 No Change
 Monitoring ultrasonic vocalizations
 10-13 months
Anxiety1
 No Change
 Elevated plus maze test: time spent in the open arms
 2-6 months
Anxiety1
 No Change
 Open field test: time spent in the center vs the periphery
 2-6 months
Anxiety3
 No Change
 Elevated zero maze test
 Adult
Cognitive flexibility1
 No Change
 Morris water maze test: reversal training phase
 2-6 months
General locomotor activity3
 No Change
 Accelerating rotarod test
 Adult
General locomotor activity3
 No Change
 Open field test
 Adult
Dendritic architecture: dendritic tree complexity1
 No Change
 Sholl analysis: Golgi-Cox staining
 P13-17, 6-8 months
Dendritic architecture: spine density1
 No Change
 Sholl analysis: Golgi-Cox staining
 P13-17, 6-8 months
Neuroreceptor levels: glutamate receptors: AMPA receptors1
 No Change
 Western blot: hippocampal lysate
 5-6 months
Neuroreceptor levels: glutamate receptors: NMDA receptors1
 No Change
 Western blot: hippocampal lysate
 5-6 months
Miniature post synaptic current amplitude: excitatory1
 No Change
 Whole-cell patch clamp
 P13-17
Presynaptic function: paired-pulse facilitation1
 No Change
 Whole-cell patch clamp
 P13-17
Synaptic plasticity: hippocampal LTD1
 No Change
 Field potential recordings
 6-8 weeks, 3-4 weeks
Self grooming: perseveration1
 No Change
 Grooming behavior assessments
 2-4.5 months
Sensorimotor gating1
 No Change
 Prepulse inhibition
 2-6 months
Startle response: acoustic stimulus1
 No Change
 Acoustic startle reflex test
 2-6 months
Social approach1
 No Change
 Three-chamber social approach test
 2-6 months
Social interaction1
 No Change
 Reciprocal social interaction test
 2-6 months
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / Ultrastructure / Cytoarchitecture, Neurophysiology, Repetitive behavior, Seizure, Sensory

M_SHANK3_8_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Dendritic architecture: dendritic tree complexity2
Increased
Description: The distal dendrites of Purkinje cells have higher complexity compared to controls in Shank3 het mice
Exp Paradigm: Males only
 Sholl analysis: Golgi-Cox staining
 2-4 months
Neuroreceptor levels: glutamate receptors: NMDA receptors1
Decreased
Description: Levesl of NR1 and NR2A are significantly reduced in the synaptosomal fraction of the frontal cortex from Shank3 het mice
Exp Paradigm: Males only
 Western blot:synaptosomal fraction of frontal cortex
 6-8 weeks
Dendritic architecture: spine density2
Decreased
Description: There is a reduction in spine density from Purkinje cell dendrites in Shank3 het mice, measured as number of spines per 10 micro meter on distal dendrites
Exp Paradigm: Males only
 Sholl analysis: Golgi-Cox staining
 2-4 months
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission1
Decreased
Description: NMDAR to AMPAR -EPSC ratio is significantly reduced in layer V pyramidal neurons of Shank3 het mice compared to wild type controls
Exp Paradigm: Males only
 Whole-cell patch clamp: layer V pyramidal neurons in the prefrontal cortex (evoked EPSC)
 6-8 weeks
Synaptic transmission: excitatory1
Decreased
Description: NMDAR dependent excitatory synaptic transmission in layer V pyramidal neurons is significantly reduced in the prefrontal cortex (PFC) of Shank3 het mice, compared to wild type.
Exp Paradigm: Males only
 Whole-cell patch clamp: layer V pyramidal neurons in the prefrontal cortex (evoked EPSC)
 6-8 weeks
EPSP-spike relationship4
Decreased
Description: Saline injected shank3-ex21-del mutant mice show reduced amplitudes of NMDAR-EPSCs induced by a series of stimulus intensities compared to saline-injected WT mice.
 Whole-cell voltage clamp: layer V pyramidal neurons of the PFC
 5-6 weeks
Synaptic transmission: excitatory1
Decreased
Description: NMDAR dependent EPSC was also reduced in the CA1 pyramidal neurons of the hippocampus in Shank3 het mice
Exp Paradigm: Males only
 Whole-cell patch clamp:CA1 pyramidal neurons (evoked EPSC)
 6-8 weeks
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission4
Decreased
Description: Saline injected shank3-ex21-del mutant mice show decreased NMDAR- to AMPAR-EPSC ratio compared to saline-injected WT mice.
 Whole-cell voltage clamp: layer V pyramidal neurons of the PFC
 5-6 weeks
Self grooming: perseveration1
Increased
Description: Shank3 het mice have increased time spent in self grooming compared to wild type controls
Exp Paradigm: Males only
 Grooming behavior assessments
 6-8 weeks
Self grooming: perseveration4
Increased
Description: Shank3 mutants with ablated exon21 showed increased self-grooming compared to controls.
 Grooming behavior assessments
 5-6 weeks
Social approach4
Decreased
Description: Shank3 mutants with ablated exon21 spend less time exploring a social stimulus compared to controls.
 Three-chamber social approach test
 5-6 weeks
Social approach1
Decreased
Description: Shank3 het mice have significantly reduced preference to social stimulus compared to wild type controls
Exp Paradigm: Males only
 Three-chamber social approach test
 6-8 weeks
Exploratory activity3
Decreased
Description: Increased avoidance behavior or decreased exploratory behavior present in both Shank3 KO and HT mice
Exp Paradigm: Decreased marble-burying in both Shank3 KO and HT mice
 Marble-burying test
 Adult
Eye blink conditioning2
Decreased
Description: Shank3 hets have significantly reduced learning of the conditioned response in eyeblink conditioning, compared to controls. The response amplitude of the eye-blink is also reduced
Exp Paradigm: Males only
 Eyeblink conditioning: probability of generating a response and response amplitude
 2-4 months
Eye blink conditioning2
Decreased
Description: Shank3 hets have a reduced reponse amplitude as well in the conditioned response, the authors state that this magnitude reflects the neural representation of the learned response
 Eyeblink conditioning: probability of generating a response
 
Cytoskeletal organization1
Decreased
Description: Similar to the decrease in F-actin in the PFC there is a reduction or loss of F actin in the hippocampus seen using phalloidin immunostaining
Exp Paradigm: Males only
 Immunostaining: hippocampal slices with phalloidin
 6-8 weeks
Protein expression level evidence4
Increased
Description: Shank3 mutants with ablated exon21 show increased protein levels of Hdac2 in the nuclear fraction of the prefrontal cortex, compared to controls.
 Western blot: nuclear fraction
 5-6 weeks
Protein-DNA complex assembly4
Increased
Description: Shank3 mutants with ablated exon21 show increased beta-catenin enrichment on the HDAC2 promoter in the PFC, implicating beta-catenin in the upregulated transcription of HDAC2.
 Chromatin immunoprecipitation (ChIP)
 5-6 weeks
Chromatin modification: Histone modification: Open chromatin4
Decreased
Description: Shank3 mutants with ablated exon21 show decreased global level of H3 acetylation in the frontal cortex than wild-type mice.
Exp Paradigm: 4??5 d post injection
 Western blot: acetylated H3
 5-8 weeks
Gene expression4
Side Effect
Description: Romidepsin injected shank3-ex21-del mutant mice show elevated levels of Cttnbp2 and Ank2, compared to controls.
 Quantitative PCR (qRT-PCR)
 5-6 weeks
Protein localization: nucleus4
Increased
Description: In the PFC of shank3 mutant mice with ablation of exon 21, the level of β-catenin in the nucleus was increased compared to controls.
 Western blot: beta-catenin
 5-6 weeks
Cytoskeletal organization4
Decreased
Description: Shank3 mutants with ablated exon21 show decrease of F-actin expression in PFC slices, indicating a loss of integrity of actin cytoskeleton at synapses.
 Immunohistochemistry: phalloidin (F-actin)
 5-6 weeks
Gene expression4
Decreased
Description: Shank3-ex21-del mutant mice show reduced levels of Arhgef7 and LIMK1 mRNA compared to controls.
 Quantitative PCR (qRT-PCR)
 5-6 weeks
Protein phosphorylation1
Decreased
Description: There is a significant reduction in protein phosphrylation levels, specifically for proteins involved in the Rac1 signaling pathway, including PAk1/2/3, LIMK and Cofilin.
Exp Paradigm: Males only
 Western blot: total lysate from PFC
 6-8 weeks
Enzyme activity1
Decreased
Description: There is decrease in the activity of Rac1/PAK1 signaling pathway enzymes including beta-PIX
Exp Paradigm: Males only
 Western blot
 6-8 weeks
Protein localization: cytosol4
Increased
Description: In the PFC of shank3 mutant mice with ablation of exon 21, the level of active (nonphosphorylated) β-catenin in the cytosol were significantly elevated, compared to controls.
 Western blot: beta-catenin
 5-6 weeks
Targeted expression4
Decreased
Description: Shank3-ex21-del mutant mice show reduced levels of Shank3 transcript and protein compared to controls.
 Quantitative PCR (qRT-PCR)
 5-6 weeks
Cytoskeletal organization1
Decreased
Description: Decrease in the inactive form of cofilin leads to decreased levels or loss of F actin determined by levels of F-actin in the synapse, even when total levels of actin in the synaptic cytosol were similar between Shank3 hets and wild type controls (PFC lysate). This was confirmed using phalloidin immunostaining in PFC slices
Exp Paradigm: Males only-Western blot: actin and F-actin levels
 Western blot: actin and F-actin levels
 6-8 weeks
Gene expression4
Increased
Description: Shank3 mutants with ablated exon21 show increased levels of HDAC2 mRNA in the prefrontal cortex compared to controls.
 Quantitative PCR (qRT-PCR)
 5-6 weeks
Protein localization: synapse4
Decreased
Description: In the PFC of shank3 mutant mice with ablation of exon 21, β-catenin at the synaptic membrane fraction was significantly reduced, compared to controls.
 Western blot: beta-catenin
 5-6 weeks
Enzyme activity1
Increased
Description: The activity of cofilin is increased following the reduction in phosphorylated (inactive) levels of cofilin as the Rac1 signaling pathway is reduced
Exp Paradigm: Males only
 Western blot
 6-8 weeks
Protein expression level evidence4
Decreased
Description: Shank3-ex21-del mutant mice show decreased protein levels of actin regulators beta-PIX (arhgef7) and LIMK1 compared to controls.
 Western blot
 5-6 weeks
Signaling1
Decreased
Description: The Rac1 signaling pathway is significantly downregulated in the prefrontal cortex of Shank3 het mice determined by the reduced levels of activated (phosphorylated) downstream effectors and increased levels of inactivated (phosphorylated) target protein cofilin.
Exp Paradigm: Males only
 Western blot: total lysate from PFC, levels of p-LIMK1, PAK1/2/3 and p-cofilin
 6-8 weeks
Cytoskeletal organization1
Decreased
Description: Decrease in the inactive form of cofilin leads to decreased levels or loss of F actin determined by levels of F-actin in the synapse, even when total levels of actin in the synaptic cytosol were similar between Shank3 hets and wild type controls (PFC lysate). This was confirmed using phalloidin immunostaining in PFC slices
Exp Paradigm: Males only- Immunostaining: phalloidin in PFC slices
 Immunostaining: phalloidin in PFC slices
 6-8 weeks
Gene expression4
Abnormal
Description: Saline-treated Shank3 mutant mice with ablated exon 21 shows a change in expression in 365 genes with values of at least 1.2-fold (213 downregulated, 152 upregulated) compared to controls.
 RNA sequencing
 5-6 weeks
Protein localization: synapse1
Decreased
Description: Based on comaprison between synaptosomal and total lysate fractions from the frontal cortex, there is reduced targeting of NR1 and NR2A NMDAR receptor subunits to the synapses in Shank3 het mice frontal cortices
Exp Paradigm: Males only
 Western blot:synaptosomal fraction and total lysate of frontal cortex
 6-8 weeks
Anxiety3
 No Change
 Elevated zero maze test
 Adult
Anxiety1
 No Change
 Open field test: time spent in the center vs the periphery
 6-8 weeks
Anxiety4
 No Change
 Open field test
 5-6 weeks
Eye blink conditioning: extinction and reactivation2
 No Change
 Eyeblink conditioning: response amplitude
 2-4 months
Spatial learning2
 No Change
 Water Y-maze test: Water Y-maze test
 2-4 months
Chromatin modification: Histone modification: Open chromatin4
 No Change
 Chromatin immunoprecipitation (ChIP)
 5-6 weeks
Chromatin modification: Histone modification: Open chromatin4
 No Change
 Chromatin immunoprecipitation (ChIP)
 5-6 weeks
Cytoskeletal organization1
 No Change
 Immunostaining: phalloidin in PFC slices
 6-8 weeks
Cytoskeletal organization1
 No Change
 Immunostaining: striatal slices with phalloidin
 6-8 weeks
Gene expression4
 No Change
 Quantitative PCR (qRT-PCR)
 5-6 weeks
Gene expression4
 No Change
 Quantitative PCR (qRT-PCR)
 5-6 weeks
Gene expression4
 No Change
 Quantitative PCR (qRT-PCR)
 5-6 weeks
Protein expression level evidence4
 No Change
 Western blot: H3
 5-8 weeks
Protein expression level evidence4
 No Change
 Western blot: nuclear fraction
 5-6 weeks
Protein expression level evidence4
 No Change
 Western blot
 5-6 weeks
Protein-DNA complex assembly4
 No Change
 Chromatin immunoprecipitation (ChIP)
 5-6 weeks
Gait2
 No Change
 Running stride analysis
 2-4 months
General locomotor activity3
 No Change
 Accelerating rotarod test
 Adult
General locomotor activity3
 No Change
 Open field test
 Adult
General locomotor activity1
 No Change
 Open field test
 6-8 weeks
General locomotor activity4
 No Change
 Novel cage test
 5-6 weeks
Motor coordination and balance1
 No Change
 Accelerating rotarod test
 6-8 weeks
Motor coordination and balance4
 No Change
 Accelerating rotarod test
 5-6 weeks
Cerebellar morphology: granule cell layer thickness2
 No Change
 Histology: Histology
 2-4 months
Cerebellar morphology: molecular layer thickness2
 No Change
 Histology: Histology
 2-4 months
Dendritic architecture: spine density1
 No Change
 Sholl analysis: Golgi-Cox staining
 6-8 weeks
Neuronal morphology4
 No Change
 Immunohistochemistry: CAMKII, NeuN
 5-6 weeks
Neuronal number in the brain4
 No Change
 Immunohistochemistry: CAMKII, NeuN
 5-6 weeks
Neuronal number: Purkinje cells2
 No Change
 Histology: Histology
 2-4 months
Neuroreceptor levels: glutamate receptors: AMPA receptors4
 No Change
 Quantitative PCR (qRT-PCR)
 5-6 weeks
Neuroreceptor levels: glutamate receptors: AMPA receptors1
 No Change
 Western blot:synaptosomal fraction and total lysate of frontal cortex
 6-8 weeks
Neuroreceptor levels: glutamate receptors: NMDA receptors4
 No Change
 Quantitative PCR (qRT-PCR)
 5-6 weeks
Neuroreceptor levels: glutamate receptors: NMDA receptors1
 No Change
 Western blot:synaptosomal fraction of frontal cortex
 6-8 weeks
Synapse density1
 No Change
 Immunostaining: PSD95
 6-8 weeks
Synaptic morphology4
 No Change
 Immunohistochemistry: PSD-95
 5-6 weeks
EPSP-spike relationship4
 No Change
 Whole-cell voltage clamp: layer V pyramidal neurons of the PFC
 5-6 weeks
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission1
 No Change
 Whole-cell patch clamp: layer V pyramidal neurons in the prefrontal cortex (evoked EPSC)
 6-8 weeks
Synaptic transmission: excitatory1
 No Change
 Whole-cell patch clamp: layer V pyramidal neurons in the prefrontal cortex (evoked EPSC)
 6-8 weeks
Synaptic transmission: excitatory1
 No Change
 Whole-cell patch clamp: medium spiny neurons of dorsal striatum
 6-8 weeks
Synaptic transmission: excitatory1
 No Change
 Whole-cell patch clamp: layer V pyramidal neurons in the prefrontal cortex (evoked EPSC)
 6-8 weeks
Self grooming: perseveration1
 No Change
 Grooming behavior assessments
 6-8 weeks
Self grooming: perseveration3
 No Change
 Grooming behavior assessments
 Adult
Social approach1
 No Change
 Three-chamber social approach test
 6-8 weeks
Social approach3
 No Change
 Three-chamber social approach test
 Adult
Social memory1
 No Change
 Three-chamber social approach test
 6-8 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Neuroanatomy / Ultrastructure / Cytoarchitecture, Neurophysiology, Repetitive behavior, Seizure, Sensory, Social behavior

M_SHANK3_10_KI_HM_InsG

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Motor coordination and balance1
Decreased
Description: Shank3G homozygous mice show reduced motor coordination and latency to fall off the accelerating rotarod
 Accelerating rotarod test
 2-6 months
Miniature post synaptic current frequency: excitatory1
Decreased
Description: The frequencey of mEPSCs in hippocampal synapses in the Shank3 mutant mice was signficantly reduced, indicatinga possible decrease in the number ofCA1 pyramidal neurons in the presence of tetradotoxin
 Whole-cell patch clamp:CA1 pyramidal neurons (evoked EPSC)
 
Synaptic plasticity: post-tetanic potentiation (PTP)1
Decreased
Description: There is a decrease in the magnitude to post-tetanic potentiation in the first five minutes following the conditioning stimulus in the hippocampal slices from Shank3G homozygous mice
 Field potential recordings: CA1 region
 
Synaptic plasticity: hippocampal LTD1
Decreased
Description: The mGluR5-LTD is reduced in magnitude in Shank3G homozygous mice in the hippocampus
 Field potential recordings: CA1 region
 
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission1
Decreased
Description: The ratio of NMDAR to AMPAR mediated EPSCs is reduced in Shank3G homozygous mice, authors indicated a reduction in NMDA mediated component of EPSC
 Whole-cell patch clamp:CA1 pyramidal neurons (evoked EPSC)
 
Synaptic transmission1
Decreased
Description: The I/O curve shows a reduced slope of fEPSP in the CA1 region
 Field potential recordings: CA1 region
 
Repetitive digging1
Decreased
Description: Shank3G homozygous mice show reduced marble-burying and the authors attribute this to increased novelty avoidance phenotype
 Marble-burying test
 2-6 months
Nest building behavior1
Decreased
Description: Shank3G homozygous mice show reduced nest building from nesting material and the authors characterize this as an increase in avoidance phenotype or response to novelty
 Nest building assay
 2-6 months
Response to novelty1
Decreased
Description: Shank3G mice show reduced response, determined by locomotor activity, compared to littermate wildtype controls in several tests when first introduced in the new environment of testing, like open field, elevated plus maze and light-dark exploration test
Exp Paradigm:  Elevated plus maze test
 Elevated plus maze test
 5-6 months
Response to novelty1
Decreased
Description: Shank3G mice show reduced response, determined by locomotor activity, compared to littermate wildtype controls in several tests when first introduced in the new environment of testing, like open field, elevated plus maze and light-dark exploration test
Exp Paradigm: Light-dark exploration test
 Light-dark exploration test: Light-dark exploration test
 5-6 months
Response to novelty1
Decreased
Description: Shank3G mice show reduced response, determined by locomotor activity, compared to littermate wildtype controls in several tests when first introduced in the new environment of testing, like open field, elevated plus maze and light-dark exploration test
Exp Paradigm:  Open field test
 Open field test
 5-6 months
Spatial learning1
Decreased
Description: Shank3G homozygous mice have reduced spatial learning in the morris water maze hidden platform task determined by distance travelled
 Morris water maze test
 2-6 months
Targeted expression1
Decreased
Description: There is loss of the wild type Shank3 protein in the homozygous Shank3G mice
 Western blot
 5-6 months
Protein phosphorylation1
Decreased
Description: Glun2B has decreased phosporylation at Ty2 1472 in the hippocampus
 Western blot: hippocampal synaptosomes
 5-6 months
Size/growth1
 No Change
 Body weight measurement
 
Anxiety1
 No Change
 Elevated plus maze test
 5-6 months
Anxiety1
 No Change
 Open field test
 5-6 months
Anxiety1
 No Change
 Light-dark exploration test: Light-dark exploration test
 5-6 months
Thigmotaxis1
 No Change
 Morris water maze test: visible platform test, hidden platform test and probe trial
 2-6 months
Spatial reference memory1
 No Change
 Morris water maze test
 2-6 months
Protein phosphorylation1
 No Change
 Western blot
 5-6 months
Neuroreceptor levels: glutamate receptors: AMPA receptors1
 No Change
 Western blot: hippocampal synaptosomes
 5-6 months
Neuroreceptor levels: glutamate receptors: NMDA receptors1
 No Change
 Western blot: hippocampal synaptosomes
 5-6 months
Synaptic neuroreceptors1
 No Change
 Western blot: hippocampal synaptosomes
 5-6 months
Decay kinetics of evoked post synaptic currents1
 No Change
 Whole-cell patch clamp:CA1 pyramidal neurons (evoked EPSC)
 
Miniature post synaptic current amplitude: excitatory1
 No Change
 Whole-cell patch clamp:CA1 pyramidal neurons (evoked EPSC)
 
Synaptic plasticity: hippocampal LTP1
 No Change
 Field potential recordings: CA1 region
 
Self grooming: perseveration1
 No Change
 Grooming behavior assessments
 2-6 months
Vision1
 No Change
 Morris water maze test: visible platform test
 2-6 months
Social approach1
 No Change
 Three-chamber social approach test
 2-6 months
Social memory1
 No Change
 Three-chamber social approach test
 2-6 months
 Not Reported: Circadian sleep/wake cycle, Communications, Homeostasis, Immune response, Maternal behavior, Seizure

M_SHANK3_10_KI_HT_InsG

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Synaptic transmission1
Decreased
Description: The I/O curve shows a reduced slope of fEPSP in the CA1 region
 Field potential recordings
 
Synaptic plasticity: hippocampal LTD1
Decreased
Description: The mGluR5-LTD is reduced in magnitude in Shank3G het mice in the hippocampus
 Field potential recordings
 
Nest building behavior1
Decreased
Description: Shank3G het mice show reduced nest building from nesting material and the authors characterize this as an increase in avoidance phenotype or response to novelty
 Nest building assay
 2-6 months
Targeted expression1
Decreased
Description: There is 50% loss of the wild type Shank3 protein in the homozygous Shank3G het mice
 Western blot
 5-6 months
Size/growth1
 No Change
 Body weight measurement
 
Anxiety1
 No Change
 Elevated plus maze test
 5-6 months
Anxiety1
 No Change
 Open field test
 5-6 months
Anxiety1
 No Change
 Light-dark exploration test: Light-dark exploration test
 5-6 months
Response to novelty1
 No Change
 Elevated plus maze test
 5-6 months
Response to novelty1
 No Change
 Open field test
 5-6 months
Response to novelty1
 No Change
 Light-dark exploration test: Light-dark exploration test
 5-6 months
Thigmotaxis1
 No Change
 Morris water maze test: visible platform test, hidden platform test and probe trial
 2-6 months
Spatial learning1
 No Change
 Morris water maze test
 2-6 months
Spatial reference memory1
 No Change
 Morris water maze test
 2-6 months
Protein phosphorylation1
 No Change
 Western blot
 5-6 months
Motor coordination and balance1
 No Change
 Accelerating rotarod test
 2-6 months
Neuroreceptor levels: glutamate receptors: AMPA receptors1
 No Change
 Western blot: hippocampal synaptosomes
 5-6 months
Neuroreceptor levels: glutamate receptors: NMDA receptors1
 No Change
 Western blot: hippocampal synaptosomes
 5-6 months
Synaptic neuroreceptors1
 No Change
 Western blot: hippocampal synaptosomes
 5-6 months
Decay kinetics of evoked post synaptic currents1
 No Change
 Whole-cell patch clamp:CA1 pyramidal neurons (evoked EPSC)
 
Miniature post synaptic current amplitude: excitatory1
 No Change
 Whole-cell patch clamp:CA1 pyramidal neurons (evoked EPSC)
 
Miniature post synaptic current frequency: excitatory1
 No Change
 Whole-cell patch clamp:CA1 pyramidal neurons (evoked EPSC)
 
Presynaptic function: presynaptic fiber volley1
 No Change
 Field potential recordings
 
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission1
 No Change
 Whole-cell patch clamp:CA1 pyramidal neurons (evoked EPSC)
 
Synaptic plasticity: hippocampal LTP1
 No Change
 Field potential recordings
 
Repetitive digging1
 No Change
 Marble-burying test
 2-6 months
Self grooming: perseveration1
 No Change
 Grooming behavior assessments
 2-6 months
Vision1
 No Change
 Morris water maze test: visible platform test
 2-6 months
Social approach1
 No Change
 Three-chamber social approach test
 2-6 months
Social memory1
 No Change
 Three-chamber social approach test
 2-6 months
 Not Reported: Circadian sleep/wake cycle, Communications, Homeostasis, Immune response, Maternal behavior, Seizure

M_SHANK3_13_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Synaptic plasticity: hippocampal LTP1
Decreased
Description: The magnitude of LTP in the CA1 region of Shank3 e4-9 HM mutants is significantly reduce compared to WT
Exp Paradigm: Males only
 Field potential recordings
 3-4 weeks
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission1
Decreased
Description: NMDAR/AMPAR mediated synaptic transmission is reduced in the medium spiny neurons of the striatum in Shank3 e4-9 HM mutants
Exp Paradigm: Males only
 Whole-cell patch clamp: striatal MSNs
 3-4 weeks
Self grooming: perseveration1
Increased
Description: Shank3 e4-9 HM mutants spend significantly increased time grooming compared to WT controls, authors note that the number of bouts was not different but the time spent in each bout was more
 Grooming behavior assessments: number of bouts and time spent in each bout of grooming
 3-5 months
Social interaction1
Decreased
Description: Shank3 e4-9 HM mutants show reduced amount of time and number of instances of interaction in the reciprocal social interaction test requiring direct interaction with stimulus adult mouse
 Reciprocal social interaction test
 3-5 months
Ultrasonic vocalization: Isolation induced1
Increased
Description: Shank3 e4-9 HM mutants make significantly more calls than WT controls (the mother is Shank3 e4-9 het) at P4 and P6
 Monitoring ultrasonic vocalizations
 P4, P6
Thigmotaxis1
Increased
Description: Shank 3 e4-9 HM mutants show a significantly higher tendency for swimming close ot the walls in the Morris water maze test compared to hets or WT controls
 Morris water maze test
 3-5 months
Spatial reference memory1
Decreased
Description: Shank3 e4-9 HM mutants show no preference to a familiar object moved to a new location, unlike WT controls
 Object-place recognition test: three objects with 5 training sessions and two test sessions where 1 object is moved to new place and another object is replaced by a novel object, repectively
 3-5 months
Object recognition memory1
Decreased
Description: Shank3 e4-9 HM mutants mice show no preference to a novel versus a familiar object
 Object-place recognition test: three objects with 5 training sessions and two test sessions where 1 object is moved to new place and another object is replaced by a novel object, repectively
 3-5 months
Targeted expression1
Decreased
Description: Shank3 e4-9 HM mutants show a complete loss of the highest mol wt. band of Shank3 protein in the striatal lysate, detected by both C and N terminal antibodies, loss of C-3, C7 and N-3 bands are also noted, HM mutants showing a loss of several isoforms of Shank3
 Western blot: whole striatal lysate and striatal synaptosomal fraction
 3-6 months
Protein localization: synapse1
Decreased
Description: Shank3 e4-9 HM mutants have decreased levels of GluA2, GluA3, Homer 1b/c and PSD95 in the synaptosomal fraction from the striatum
 Western blot:striatal synaptosomal fraction
 3-6 months
Anxiety1
 No Change
 Elevated plus maze test
 3-5 months
Anxiety1
 No Change
 Light-dark exploration test: Light-dark exploration test
 3-5 months
Anxiety1
 No Change
 Marble-burying test
 3-5 months
Anxiety1
 No Change
 Open field test
 3-5 months
Cognitive flexibility1
 No Change
 Morris water maze test
 
Cued or contextual fear conditioning1
 No Change
 Fear conditioning test
 
Spatial learning1
 No Change
 Morris water maze test
 3-5 months
Spatial reference memory1
 No Change
 Morris water maze test
 3-5 months
Protein localization: synapse1
 No Change
 Western blot:striatal synaptosomal fraction
 3-6 months
General locomotor activity1
 No Change
 Open field test
 
Motor coordination and balance1
 No Change
 Accelerating rotarod test
 
Miniature post synaptic current amplitude: excitatory1
 No Change
 Whole-cell patch clamp: striatal MSNs
 3-4 weeks
Miniature post synaptic current amplitude: excitatory1
 No Change
 Whole-cell patch clamp: hippocampal CA1
 P14-P17
Miniature post synaptic current frequency: excitatory1
 No Change
 Whole-cell patch clamp: striatal MSNs
 3-4 weeks
Miniature post synaptic current frequency: excitatory1
 No Change
 Whole-cell patch clamp: hippocampal CA1
 P14-P17
Presynaptic function: paired-pulse facilitation1
 No Change
 Paired-pulse ratio
 P14-P17
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission1
 No Change
 Whole-cell patch clamp: hippocampus
 P14-P17
Synaptic plasticity: hippocampal LTD1
 No Change
 Field potential recordings
 3-4 weeks
Synaptic transmission: excitatory1
 No Change
 Field potential recordings
 3-4 weeks
Sensorimotor gating1
 No Change
 Prepulse inhibition
 3-5 months
Startle response: acoustic stimulus1
 No Change
 Acoustic startle reflex test
 3-5 months
Vision1
 No Change
 Morris water maze test
 3-5 months
Nest building behavior1
 No Change
 Nest building assay
 3-5 months
Social interaction1
 No Change
 Partition test
 3-5 months
Social interaction: with juveniles1
 No Change
 Reciprocal social interaction test
 3-5 months
Social memory1
 No Change
 Reciprocal social interaction test: interaction with familiar juvenile mouse
 3-5 months
 Not Reported: Circadian sleep/wake cycle, Developmental profile, Homeostasis, Immune response, Maternal behavior, Neuroanatomy / Ultrastructure / Cytoarchitecture, Seizure

M_SHANK3_13_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission1
Decreased
Description: NMDAR/AMPAR mediated synaptic transmission is reduced in the medium spiny neurons of the striatum in Shank3 e4-9 het mutants
Exp Paradigm: Males only
 Whole-cell patch clamp: striatal MSNs
 3-4 weeks
Self grooming: perseveration1
Increased
Description: Shank3 e4-9 het mutants spend significantly increased time grooming compared to WT controls, authors note that the number of bouts was not different but the time spent in each bout was more
 Grooming behavior assessments: number of bouts and time spent in each bout of grooming
 3-5 months
Ultrasonic vocalization: Isolation induced1
Increased
Description: Shank3 e4-9 Het mutants make significantly increased number of calls compared to WT controls at P4 and P12
 Monitoring ultrasonic vocalizations
 P4, P12
Spatial reference memory1
Decreased
Description: Shank3 e4-9 Het mutants have no preference for a familiar object moved to a new location, unlike WT controls indicating reduced reference memory in the Object-place recognition test
 Object-place recognition test: three objects with 5 training sessions and two test sessions where 1 object is moved to new place and another object is replaced by a novel object, repectively
 3-5 months
Object recognition memory1
Decreased
Description: Shank3 e4-9 Het mutants have no preference for novel object that replaces a familiar object
 Object-place recognition test: three objects with 5 training sessions and two test sessions where 1 object is moved to new place and another object is replaced by a novel object, repectively
 3-5 months
Targeted expression1
Decreased
Description: Shank3 e4-9 Het mutants have reduced levels of highest molecular weight bands of Shank 3 protein as expected in heterozygotes
 Western blot: whole striatal lysate and striatal synaptosomal fraction
 3-6 months
Anxiety1
 No Change
 Elevated plus maze test
 3-5 months
Anxiety1
 No Change
 Light-dark exploration test: Light-dark exploration test
 3-5 months
Anxiety1
 No Change
 Marble-burying test
 3-5 months
Anxiety1
 No Change
 Open field test
 3-5 months
Thigmotaxis1
 No Change
 Morris water maze test
 3-5 months
Cognitive flexibility1
 No Change
 Morris water maze test
 3-5 months
Cued or contextual fear conditioning1
 No Change
 Fear conditioning test
 
Spatial learning1
 No Change
 Morris water maze test
 3-5 months
Spatial reference memory1
 No Change
 Morris water maze test
 3-5 months
Protein localization: synapse1
 No Change
 Western blot:striatal synaptosomal fraction
 3-6 months
General locomotor activity1
 No Change
 Open field test
 3-5 months
Motor coordination and balance1
 No Change
 Accelerating rotarod test
 3-5 months
Miniature post synaptic current amplitude: excitatory1
 No Change
 Whole-cell patch clamp: striatal MSNs
 3-4 weeks
Miniature post synaptic current amplitude: excitatory1
 No Change
 Whole-cell patch clamp: hippocampal CA1
 P14-P17
Miniature post synaptic current frequency: excitatory1
 No Change
 Whole-cell patch clamp: striatal MSNs
 3-4 weeks
Miniature post synaptic current frequency: excitatory1
 No Change
 Whole-cell patch clamp: hippocampal CA1
 P14-P17
Presynaptic function: paired-pulse facilitation1
 No Change
 Paired-pulse ratio
 3-4 weeks
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission1
 No Change
 Whole-cell patch clamp: hippocampus
 P14-P17
Synaptic plasticity: hippocampal LTD1
 No Change
 Field potential recordings
 3-4 weeks
Synaptic plasticity: hippocampal LTP1
 No Change
 Field potential recordings
 3-4 weeks
Synaptic transmission: excitatory1
 No Change
 Field potential recordings
 3-4 weeks
Sensorimotor gating1
 No Change
 Prepulse inhibition
 3-5 months
Startle response: acoustic stimulus1
 No Change
 Acoustic startle reflex test
 3-5 months
Vision1
 No Change
 Morris water maze test
 3-5 months
Nest building behavior1
 No Change
 Nest building assay
 3-5 months
Social interaction1
 No Change
 Partition test
 3-5 months
Social interaction1
 No Change
 Reciprocal social interaction test
 3-5 months
Social interaction: with juveniles1
 No Change
 Reciprocal social interaction test
 3-5 months
Social memory1
 No Change
 Reciprocal social interaction test
 3-5 months
 Not Reported: Circadian sleep/wake cycle, Developmental profile, Homeostasis, Immune response, Maternal behavior, Neuroanatomy / Ultrastructure / Cytoarchitecture, Seizure

M_SHANK3_15_KI_HM_InsG

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Motor coordination and balance1
Decreased
Description: Shank3 InsG HM mice have shorter latencies to fall off in the accelrating rotarod test compared to WT
 Accelerating rotarod test
 Adult
General locomotor activity1
Decreased
Description: Shank3 InsG HM mice have reduced general locomotor activity in the open field compared to WT
 Open field test
 Adult
Neuroreceptor levels: glutamate receptors: AMPA receptors1
Decreased
Description: GluR2 and mGluR5 levels are decreased in Shank3 InsG HM mutants
 Western blot: striatal synaptic membrane protein receptors
 Adult
Dendritic architecture: spine density1
Decreased
Description: Shank3 InsG HM mutants had reduced dendritic spine density in layer 2/3 pyramidal neurons in the 'frontal association area', compared to WT
 Golgi-Cox staining
 2 months
Neuroreceptor levels: glutamate receptors: NMDA receptors1
Decreased
Description: NR1, NR2A and NR2B levels are decreased in Shank3 InsG HM mutants
 Western blot: striatal synaptic membrane protein receptors
 Adult
Neuroreceptor levels: glutamate receptors: AMPA receptors1
Increased
Description: Shank3 InsG have increased levels of GluR1, corresponding to increased amplitude of mEPSCs, at P14, compared to WT
 Western blot: striatal synaptic membrane protein receptors
 P14
Population spikes1
Decreased
Description: Shank3 InsG HM mutants had reduced evoked population spikes in the striatum compared to WT
 Field potential recordings: striatum
 Adult
Miniature post synaptic current amplitude: excitatory1
Decreased
Description: AMPAR mediated mEPSC frequency and amplitude are reduced significantly in Shank3 InsG HM adult mice
 Whole-cell patch clamp: AMPAR mediated currents in striatal MSNs
 Adult
Miniature post synaptic currents: excitatory1
Decreased
Description: NMDAR mediated mEPSCs are reduced in Shank3 InsG HM adults as well
 Whole-cell patch clamp: NMDAR mediated currents in striatal MSNs
 Adult
Miniature post synaptic current frequency: excitatory1
Decreased
Description: AMPAR mediated mEPSC frequency and amplitude are reduced significantly in Shank3 InsG HM adult mice
 Whole-cell patch clamp: AMPAR mediated currents in striatal MSNs
 Adult
Population spikes1
Decreased
Description: Shank3 InsG HM mutants had reduced evoked population spikes in the striatum compared to WT
 Field potential recordings: striatum
 P14
Miniature post synaptic current amplitude: excitatory1
Increased
Description: At P14, Shank3 InsG HM mutants have increased amplitude of AMPA mediated mEPSCs in the dorsolateral striatal MSNs from WT
 Whole-cell patch clamp: AMPAR mediated currents in striatal MSNs
 P14
Self grooming: perseveration1
Increased
Description: Shank3 InsG mutants spend almost twice as much time grooming compared to WT controls
 Grooming behavior assessments
 Adult
Sensorimotor gating1
Decreased
Description: Shank3 InsG have impaired prepulse inhibition compared to WT
 Prepulse inhibition
 Adult
Startle response: acoustic stimulus1
Decreased
Description: Shank3 InsG have significantly impaired acoustic startle reflex and authors note that this complicated interpretation of PPI data
 Acoustic startle reflex test
 Adult
Social dominance1
Increased
Description: Shank3InsG HM mutants have a higher propensity of winning in a social confrontation in the tube test
 Tube test of social dominance
 Adult
Social approach1
Decreased
Description: Shank3 InsG HM mutants display no preference for a stimilus mouse over an object, unlike WT controls
 Three-chamber social approach test
 Adult
Juvenile play1
Decreased
Description: Shank3 InsG HM mutants show reduction in juvenile play with reduced nose-anogenital sniffing and following behavior compared to WT
 Reciprocal social interaction test
 3 weeks
Social memory1
Decreased
Description: Shank3 InsG HM mutants display no preference for a stranger mouse over a familiar mouse unlike WT controls
 Three-chamber social approach test
 Adult
Anxiety1
Increased
Description: Shank3 InsG HM mutants have increased anxiety-like behavior as they spend reduced time in center in the open field and in the open arms of the elevated zero maze
Exp Paradigm:  Elevated zero maze test
 Elevated zero maze test
 Adult
Exploratory activity1
Decreased
Description: Shank3 InsG HM mutants have decreased exploratory activity in an environment determined by the amount of distance traveled
 Open field test
 Adult
Anxiety1
Increased
Description: Shank3 InsG HM mutants have increased anxiety-like behavior as they spend reduced time in center in the open field and in the open arms of the elevated zero maze
Exp Paradigm: Open field test
 Open field test
 Adult
Protein localization: synapse1
Decreased
Description: Shank3 InsG HM mice have decreased levels of Homer 1b-c, PSD 95 and 93 in the cortial synaptic membrane prep from adult mice
 Western blot: cortical synaptic membrane protein receptors
 Adult
Gene expression1
Increased
Description: Shank2 and Shank2 mRNAs are increased in the cortical tissue of Shank3 InsG HM mutants
 Quantitative PCR (qRT-PCR): cortical tissue
 2 months
Targeted expression1
Decreased
Description: Shank3 InsG HM mutation results in loss of WT Shank3 and even the expected 135 kDa band of the truncated protein is also not detected in western blots, Shank3 mRNA levels are also severely reduced indicating possible degradation via the nonsense mediated decay
Exp Paradigm: Western blot: striatal lysate
 Western blot: striatal lysate
 2 months
Protein localization: synapse1
Decreased
Description: Shank3 InsG have decreased Homer at P14 in the striatal synaptosomal preparations compared to WT
 Western blot: striatal synaptic membrane proteins
 P14
Targeted expression1
Decreased
Description: Shank3 InsG HM mutation results in loss of WT Shank3 and even the expected 135 kDa band of the truncated protein is also not detected in western blots, Shank3 mRNA levels are also severely reduced indicating possible degradation via the nonsense mediated decay
Exp Paradigm:  Quantitative PCR (qRT-PCR)
 Quantitative PCR (qRT-PCR)
 2 months
Protein localization: synapse1
Increased
Description: Increased levels of Shank2 proteins are observed in Shank3 InsG HM mutants
 Western blot: cortical synaptic membrane protein receptors
 P14
Protein localization: synapse1
Decreased
Description: Shank3 InsG mutants have decreased levels of Homer 1b-c and Syngap1, Sapap3 in the striatal synaptosomal plasma membrane prep
 Western blot: striatal synaptic membrane proteins
 Adult
Protein expression level evidence1
Increased
Description: Shank2 protein levels are increased in the cortical tissue of Shank3 InsG HM mutants
 Western blot: cortical tissue
 2 months
Ultrasonic vocalization: Isolation induced1
 No Change
 Monitoring ultrasonic vocalizations: number, duration, peak amplitude of calls
 P2-P12
Exploratory activity: Habituation1
 No Change
 Open field test
 Adult
Spatial working memory1
 No Change
 T-maze test
 Adult
Protein localization: synapse1
 No Change
 Western blot: cortical synaptic membrane protein receptors
 P14
Neuroreceptor levels: glutamate receptors: AMPA receptors1
 No Change
 Western blot: cortical synaptic membrane protein (SPM) receptors
 P14
Neuroreceptor levels: glutamate receptors: AMPA receptors1
 No Change
 Western blot: cortical synaptic membrane protein receptors
 Adult
Neuroreceptor levels: glutamate receptors: NMDA receptors1
 No Change
 Western blot: cortical synaptic membrane protein receptors
 P14
Neuroreceptor levels: glutamate receptors: NMDA receptors1
 No Change
 Western blot: cortical synaptic membrane protein receptors
 Adult
Miniature post synaptic current amplitude: excitatory1
 No Change
 Whole-cell patch clamp: pyramidal neurons of mPFC
 Adult
Miniature post synaptic current amplitude: excitatory1
 No Change
 Whole-cell patch clamp: pyramidal neurons of mPFC
 P14
Miniature post synaptic current frequency: excitatory1
 No Change
 Whole-cell patch clamp: AMPAR mediated currents in striatal MSNs
 P14
Miniature post synaptic current frequency: excitatory1
 No Change
 Whole-cell patch clamp: pyramidal neurons of mPFC
 Adult
Miniature post synaptic current frequency: excitatory1
 No Change
 Whole-cell patch clamp: pyramidal neurons of mPFC
 P14
Presynaptic function1
 No Change
 Field potential recordings: striatum, negative peak1 measurement
 P14, adult
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission1
 No Change
 Whole-cell patch clamp: AMPAR mediated currents in striatal MSNs
 P14
 Not Reported: Circadian sleep/wake cycle, Developmental profile, Homeostasis, Immune response, Maternal behavior, Seizure

M_SHANK3_15_KI_HT_InsG

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
General locomotor activity1
Decreased
Description: Shank3 InsG HT mutants display decreased distance traveled in the open field compared to WT indicating reduced activity
 Open field test
 Adult
Miniature post synaptic current frequency: excitatory1
Decreased
Description: Shank3 InsG HT mutants have decreased frequency of AMPAR mediated mEPSCs in the dorsostriatal MSNs
 Whole-cell patch clamp: AMPAR mediated currents in striatal MSNs
 Adult
Anxiety1
Increased
Description: Shank3 InsG HT mutants have increased anxiety-like behavior as they spend less time in the open arms compared to WT
 Elevated zero maze test
 Adult
Exploratory activity1
Decreased
Description: Shank3 InsG HT mutants have significantly reduced distance traveled compared to WT in the open field test indicating decrease in exploratory activity
 Open field test
 Adult
Targeted expression1
Decreased
Description: There is 50% reduction in WT Shank3 protein in Shank3 InsG HT mice
 Western blot: striatal synaptic membrane proteins
 2 months
Protein localization: synapse1
Decreased
Description: Shank3 InsG HT mutants have reduced Homer protein in the synaptosomal plasma membrane preparation from the striatum
 Western blot: striatal synaptic membrane proteins
 Adult
Targeted expression1
Decreased
Description: There is 50% reduction in WT Shank3 protein in Shank3 R-X HT mice
 Western blot: striatal synaptic membrane proteins
 2 months
Exploratory activity: Habituation1
 No Change
 Open field test
 Adult
Motor coordination and balance1
 No Change
 Accelerating rotarod test
 Adult
Dendritic architecture: spine density1
 No Change
 Golgi-Cox staining
 2 months
Miniature post synaptic current amplitude: excitatory1
 No Change
 Whole-cell patch clamp: AMPAR mediated currents in striatal MSNs
 Adult
Miniature post synaptic current amplitude: excitatory1
 No Change
 Whole-cell patch clamp: pyramidal neurons of mPFC
 Adult
Miniature post synaptic current frequency: excitatory1
 No Change
 Whole-cell patch clamp: pyramidal neurons of mPFC
 Adult
Population spikes1
 No Change
 Field potential recordings: striatum
 Adult
Presynaptic function1
 No Change
 Field potential recordings: striatum, negative peak1 measurement
 Adult
Allogrooming: perseveration1
 No Change
 Grooming behavior assessments
 Adult
Self grooming: perseveration1
 No Change
 Grooming behavior assessments
 5 months
Sensorimotor gating1
 No Change
 Prepulse inhibition
 Adult
Startle response: acoustic stimulus1
 No Change
 Acoustic startle reflex test
 Adult
Social approach1
 No Change
 Three-chamber social approach test
 Adult
Social dominance1
 No Change
 Tube test of social dominance
 Adult
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Homeostasis, Immune response, Learning & memory, Maternal behavior, Seizure

M_SHANK3_17_KI_HM_R1117X

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Motor coordination and balance1
Decreased
Description: Shank3 InsG HM mice have shorter latencies to fall off in the accelrating rotarod test compared to WT
 Accelerating rotarod test
 Adult
General locomotor activity1
Decreased
Description: Shank3 InsG HM mice have reduced general locomotor activity in the open field compared to WT
 Open field test
 Adult
Neuroreceptor levels: glutamate receptors: NMDA receptors1
Decreased
Description: There is decrease in the levels of NR1 and its partner Syngap1 in the cortical SPM prep from Shank3 R-X HM mutant mice
 Western blot: cortical synaptic membrane protein receptors
 Adult
Neuroreceptor levels: glutamate receptors: NMDA receptors1
Decreased
Description: NR1, NR2A and NR2B levels are decreased in Shank3 R-X HM mutants
 Western blot: striatal synaptic membrane protein receptors
 Adult
Neuroreceptor levels: glutamate receptors: AMPA receptors1
Decreased
Description: GluR2 and mGluR5 levels are decreased in Shank3 R-X HM mutants
 Western blot: striatal synaptic membrane protein receptors
 Adult
Dendritic architecture: spine density1
Decreased
Description: Shank3 R-X HM mutants had reduced dendritic spine density in layer 2/3 pyramidal neurons in the 'frontal association area', compared to WT
 Golgi-Cox staining
 2 months
Population spikes1
Decreased
Description: Shank3 R-X HM mutants have reduced evoked population spikes compared to WT in the striatum in adult mice, unlike at P14
 Field potential recordings: striatum
 Adult
Miniature post synaptic current frequency: excitatory1
Decreased
Description: AMPAR mediated mEPSC frequency and amplitude are reduced significantly in Shank3 R-X HM adult mice
 Whole-cell patch clamp: AMPAR mediated currents in striatal MSNs
 Adult
Miniature post synaptic currents: excitatory1
Decreased
Description: NMDAR mediated mEPSCs are reduced in Shank3 InsG HM adults as well
 Whole-cell patch clamp: NMDAR mediated currents in striatal MSNs
 Adult
Miniature post synaptic current amplitude: excitatory1
Decreased
Description: Miniature EPSC frequency and amplitude are both reduced Shank3 R-X HM mutants (this mutation is reported in schizophrenia patients) in the pyramidal neurons of the prefrontal cortex
 Whole-cell patch clamp: pyramidal neurons of mPFC
 Adult
Miniature post synaptic current frequency: excitatory1
Decreased
Description: Miniature EPSC frequency and amplitude are both reduced Shank3 R-X HM mutants (this mutation isreported in schizophrenia patients) in the pyramidal neurons of the prefrontal cortex
 Whole-cell patch clamp: pyramidal neurons of mPFC
 Adult
Miniature post synaptic current amplitude: excitatory1
Decreased
Description: AMPAR mediated mEPSC frequency and amplitude are reduced significantly in Shank3 R-X HM adult mice
 Whole-cell patch clamp: AMPAR mediated currents in striatal MSNs
 Adult
Miniature post synaptic current frequency: excitatory1
Increased
Description: Miniature EPSC amplitude is increased in Shank3 R-X HM mutants in the pyramidal neurons of the prefrontal cortex at P14
 Whole-cell patch clamp: pyramidal neurons of mPFC
 P14
Startle response: acoustic stimulus1
Decreased
Description: Shank3 R-X have significantly impaired acoustic startle reflex and authors note that this complicated interpretation of PPI data
 Acoustic startle reflex test
 Adult
Sensorimotor gating1
Decreased
Description: Shank3 R-X have impaired prepulse inhibition compared to WT
 Prepulse inhibition
 Adult
Social approach1
Decreased
Description: Shank3 R-X HM mutants display no preference for a stimulus mouse over an object, unlike WT controls
 Three-chamber social approach test
 Adult
Social memory1
Decreased
Description: Shank3 R-X HM mutants display no preference for a stranger mouse over a familiar mouse unlike WT controls
 Three-chamber social approach test
 Adult
Social dominance1
Increased
Description: Shank3 R-X HM mutants have a higher propensity of winning in a social confrontation in the tube test
 Tube test of social dominance
 Adult
Anxiety1
Increased
Description: Shank3 R-X HM mutants have increased anxiety-like behavior as they spend reduced time in center in the open field and in the open arms of the elevated zero maze
Exp Paradigm:  Elevated zero maze test
 Elevated zero maze test
 Adult
Exploratory activity1
Decreased
Description: Shank3 R-X HM mutants have decreased exploratory activity in an environment determined by the amount of distance traveled
 Open field test
 Adult
Anxiety1
Increased
Description: Shank3 R-X HM mutants have increased anxiety-like behavior as they spend reduced time in center in the open field and in the open arms of the elevated zero maze
Exp Paradigm: Open field test
 Open field test
 Adult
Targeted expression1
Decreased
Description: Shank3 R-X HM mutation results in the production of the 122kDa truncated protein that is expected following the mutation, detected using a N term antibody, while the SHank3 mRNA is detected at a higher levels than in InsG mutants
Exp Paradigm:  Quantitative PCR (qRT-PCR)
 Quantitative PCR (qRT-PCR)
 2 months
Protein localization: synapse1
Decreased
Description: Shank3 R-X HM have decreased Homer protein at P14 in the striatal synaptosomal preparations compared to WT
 Western blot: striatal synaptic membrane proteins
 P14
Protein localization: synapse1
Decreased
Description: Shank3 R-X HM mutants have slight but significant decrease in Homer protein in the cortical synaptic membrane preparation at P14
 Western blot: cortical synaptic membrane protein receptors
 P14
Protein localization: synapse1
Decreased
Description: Shank3 R-X HM mutants have decreased levels of Homer 1b-c and Syngap1, Sapap3 in the striatal synaptosomal plasma membrane prep
 Western blot: striatal synaptic membrane proteins
 Adult
Targeted expression1
Decreased
Description: Shank3 R-X HM mutation results in the production of the 122kDa truncated protein that is expected following the mutation, detected using a N term antibody, while the SHank3 mRNA is detected at a higher levels than in InsG mutants
Exp Paradigm: Western blot: striatal lysate
 Western blot: striatal lysate
 2 months
Protein localization: synapse1
Decreased
Description: Shank3 R-X HM mice have decreased levels of Homer 1b-c, PSD 95 and 93 in the cortial synaptic membrane prep from adult mice
 Western blot: cortical synaptic membrane protein receptors
 Adult
Ultrasonic vocalization: Isolation induced1
 No Change
 Monitoring ultrasonic vocalizations: number, duration, peak amplitude of calls
 P2-P12
Exploratory activity: Habituation1
 No Change
 Open field test
 Adult
Spatial working memory1
 No Change
 T-maze test
 Adult
Gene expression1
 No Change
 Quantitative PCR (qRT-PCR): cortical tissue
 2 months
Protein expression level evidence1
 No Change
 Western blot: cortical tissue
 2 months
Protein localization: synapse1
 No Change
 Western blot: cortical synaptic membrane protein receptors
 P14
Neuroreceptor levels: glutamate receptors: AMPA receptors1
 No Change
 Western blot: striatal synaptic membrane protein receptors
 P14
Neuroreceptor levels: glutamate receptors: AMPA receptors1
 No Change
 Western blot: cortical synaptic membrane protein receptors
 P14
Neuroreceptor levels: glutamate receptors: AMPA receptors1
 No Change
 Western blot: cortical synaptic membrane protein receptors
 Adult
Neuroreceptor levels: glutamate receptors: NMDA receptors1
 No Change
 Western blot: cortical synaptic membrane protein receptors
 P14
Miniature post synaptic current amplitude: excitatory1
 No Change
 Whole-cell patch clamp: AMPAR mediated currents in striatal MSNs
 P14
Miniature post synaptic current amplitude: excitatory1
 No Change
 Whole-cell patch clamp: pyramidal neurons of mPFC
 P14
Miniature post synaptic current frequency: excitatory1
 No Change
 Whole-cell patch clamp: AMPAR mediated currents in striatal MSNs
 P14
Population spikes1
 No Change
 Field potential recordings: striatum
 P14
Presynaptic function1
 No Change
 Field potential recordings: straitum
 P14, adult
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission1
 No Change
 Whole-cell patch clamp: AMPAR mediated currents in striatal MSNs
 P14
Self grooming: perseveration1
 No Change
 Grooming behavior assessments
 5 months
Juvenile play1
 No Change
 Reciprocal social interaction test
 3 weeks
 Not Reported: Circadian sleep/wake cycle, Developmental profile, Homeostasis, Immune response, Maternal behavior, Seizure

M_SHANK3_17_KI_HT_R1117X

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Dendritic architecture: spine density1
Decreased
Description: SHank3 R-X HT mutants have reduced spine density in layer 2/3 pyramidal neurons
 Golgi-Cox staining
 2 months
Miniature post synaptic current amplitude: excitatory1
Decreased
Description: Shank3 R-X HT mutants have small but significant decrease in the amplitude of AMPAR mediated mEPSCs in the dorsostriatal MSNs
 Whole-cell patch clamp: AMPAR mediated currents in striatal MSNs
 Adult
Miniature post synaptic current frequency: excitatory1
Decreased
Description: Shank3 R-X HT mutants have significant reduction in the amplitude of AMPAR mediated mEPSCs in the dorsostriatal MSNs
 Whole-cell patch clamp: pyramidal neurons of mPFC
 Adult
Allogrooming: perseveration1
Increased
Description: Shank3 R-X HT mutants show increased propensity of allogrooming cage mates than WT
 Grooming behavior assessments
 Adult
Social dominance1
Increased
Description: Shank3 R-X HT mutants show increased dominant behavior and propensity of winning in social confrontation in the tube test than WT
 Tube test of social dominance
 Adult
Social approach1
Decreased
Description: Shank3 R-X HT mutants show decreased sociability and preference for social target compared to an object in the three chamber test
 Three-chamber social approach test
 Adult
Anxiety1
Increased
Description: Shank3 R-X HT mutants have increased anxiety-like behavior in the OF
 Elevated zero maze test: time spent in open arms
 Adult
Protein localization: synapse1
Decreased
Description: Shank3 R-X HT mutants have reduced Homer protein in the synaptosomal plasma membrane preparation from the striatum
 Western blot: striatal synaptic membrane proteins
 Adult
Exploratory activity1
 No Change
 Open field test: distance traveled
 Adult
Exploratory activity: Habituation1
 No Change
 Open field test
 Adult
General locomotor activity1
 No Change
 Open field test
 Adult
Motor coordination and balance1
 No Change
 Accelerating rotarod test
 Adult
Miniature post synaptic current amplitude: excitatory1
 No Change
 Whole-cell patch clamp: pyramidal neurons of mPFC
 Adult
Miniature post synaptic current frequency: excitatory1
 No Change
 Whole-cell patch clamp: AMPAR mediated currents in striatal MSNs
 Adult
Population spikes1
 No Change
 Field potential recordings: striatum
 Adult
Presynaptic function1
 No Change
 Field potential recordings: striatum, negative peak1 measurement
 Adult
Self grooming: perseveration1
 No Change
 Grooming behavior assessments
 Adult
Sensorimotor gating1
 No Change
 Prepulse inhibition
 Adult
Startle response: acoustic stimulus1
 No Change
 Acoustic startle reflex test
 Adult
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Homeostasis, Immune response, Learning & memory, Maternal behavior, Seizure

M_SHANK3_21_KI_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Motor coordination and balance1
Decreased
Description: Mutants show decreased motor coordination compared to controls.
Exp Paradigm: Latency to fall was the measured parameter.
 Accelerating rotarod test
 Unreported
General locomotor activity: Ambulatory activity1
Decreased
Description: Mutants show decreased ambulatory activity compared to controls.
 Open field test
 Unreported
Population spikes1
Decreased
Description: Mutants show decreased field population spikes in the dorsal striatum compared to controls.
 Field potential recordings
 3-7 months
Miniature post synaptic current frequency: excitatory1
Decreased
Description: Mutants show no change in mEPSC amplitude in the striatum compared to controls.
 Whole-cell patch clamp
 3-7 months
Miniature post synaptic current amplitude: excitatory1
Decreased
Description: Mutants show decreased mEPSC amplitude in the striatum compared to controls.
 Whole-cell patch clamp
 3-7 months
Self grooming: perseveration1
Increased
Description: Mutants show increased self grooming compared to controls.
Exp Paradigm: Self-grooming was assessed by observing wound lesions.
 General observations
 Unreported
Anxiety1
Increased
Description: Mutants show increased anxiety compared to controls.
Exp Paradigm: Recordings were made in 5-min intervals.
 Zero maze test
 Unreported
Targeted expression1
Decreased
Description: Mutants show decreased expression of major isoforms of SHANK3 protein (alpha, beta and gamma), compared to controls.
 Western blot
 Unreported
Miniature post synaptic current amplitude: excitatory1
 No Change
 Whole-cell patch clamp
 3-7 months
Miniature post synaptic current frequency: excitatory1
 No Change
 Whole-cell patch clamp
 3-7 months
Presynaptic function: paired-pulse facilitation1
 No Change
 Whole-cell patch clamp
 3-7 months, P20-21
Presynaptic function: presynaptic fiber volley1
 No Change
 Field potential recordings
 3-7 months
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission1
 No Change
 Whole-cell patch clamp
 3-7 months
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Homeostasis, Immune response, Learning & memory, Maternal behavior, Neuroanatomy / Ultrastructure / Cytoarchitecture, Seizure, Sensory, Social behavior

M_SHANK3_22_KI_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Motor coordination and balance1
Decreased
Description: Mutants show decreased latency to fall compared to controls.
 Accelerating rotarod test
 Adult, P20-21
General locomotor activity: Ambulatory activity1
Decreased
Description: Mutants show decrease in total distance travelled compared to controls.
 Open field test
 Adult, P20-21
Dendritic architecture: spine density1
Decreased
Description: Mutants show decreased spine density in the medium spiny neurons of the striatum compared to controls.
Exp Paradigm: Used systemic viral injection to sparsely label neurons with green fluorescent protein.
 Immunohistochemistry: AAV-GFP labeling
 Adult, P20-21
Population spikes1
Decreased
Description: Mutants show decreased field population spikes in the dorsal striatum compared to controls.
 Field potential recordings
 3-7 months
Miniature post synaptic current frequency: excitatory1
Decreased
Description: Mutants show decrease in mEPSC frequency in the dorsal striatum compared to controls.
 Whole-cell patch clamp
 3-7 months, P20-21
Self grooming: perseveration1
Increased
Description: Mutants show increased self grooming compared to controls.
 Grooming behavior assessments
 Adult, P20-21
Social approach1
Decreased
Description: Mutants showed no difference in time spent with the stranger mouse or the novel object, in contrast to wildtype mice that spent more time with the stranger mouse than with the novel object.
Exp Paradigm: S129 males were used as stranger mice.
 Three-chamber social approach test
 Adult, P20-21
Rearing behavior1
Decreased
Description: Mutants show decreased rearing time and frequency compared to controls.
 Open field test
 
Size/growth1
Decreased
Description: Mutants show decreased body weight compared to controls.
 Body weight measurement
 P20-21
Anxiety1
Increased
Description: Mutants show decrease in time spent in open arms compared to controls.
Exp Paradigm: Recordings were made in 5-min intervals.
 Elevated zero maze test
 Adult, P20-21
Protein expression level evidence1
Increased
Description: Mutants show increased expression of Shank2 in the cortex compared to controls.
 Western blot
 Adult, P20-21
Protein expression level evidence1
Decreased
Description: Mutants show decreased expression of postsynaptic density proteins, SAPAP3, Homer1b/c, NR2A, NR2B and GluA2 in the striatum, compared to controls. Mutants show decreased expression of GluA1 in the cerebellum compared to controls.
Exp Paradigm: Western blots of striatal synaptosomal fractions of the striatum were performed.
 Western blot
 Adult, P20-21
Targeted expression1
Decreased
Description: Mutants show decreased expression of Shank3 in the striatum, cortex and cerebellum compared to controls.
Exp Paradigm: Western blots of striatal synaptosomal fractions of the striatum, cortex and cerebellum were performed.
 Western blot
 Adult, P20-21
Protein expression level evidence1
 No Change
 Western blot
 Adult, P20-21
Neuroreceptor levels: glutamate receptors: NMDA receptors1
 No Change
 Whole-cell patch clamp
 3-7 months, P20-21
Miniature post synaptic current amplitude: excitatory1
 No Change
 Whole-cell patch clamp
 3-7 months, P20-21
Presynaptic function: paired-pulse facilitation1
 No Change
 Whole-cell patch clamp
 3-7 months, P20-21
Presynaptic function: presynaptic fiber volley1
 No Change
 Field potential recordings
 3-7 months
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission1
 No Change
 Whole-cell patch clamp
 3-7 months, P20-21
 Not Reported: Circadian sleep/wake cycle, Communications, Homeostasis, Immune response, Learning & memory, Maternal behavior, Seizure, Sensory

M_SHANK3_19_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Self grooming: artificial stress evoked1
Increased
Description: Increased grooming is observed after splashing in Shank3 nulls (tested in Shank3 null mice that did not develop lesions)
Exp Paradigm: splashing test conducted in mice that did not show excessive self grooming behavior in home cage
 Grooming behavior assessments
 4-7 months
Motor coordination and balance1
Decreased
Description: Shank3 null mice display a reduced latency to fall off steady state or accelerating rotarod
 Accelerating rotarod test
 >2 months
General locomotor activity: Ambulatory activity1
Decreased
Description: Shank3 null mice are hypoactive in their home cage
 Home cage behavior
 Adult
General locomotor activity1
Decreased
Description: Shank3 null mice display hypoactivity, with reduced rearing and locomotion in open field test as well
 Open field test
 Adult
Morphology and size of the corpus callosum1
Decreased
Description: Corpus callosum is smaller in Shank3 null mice
 Voxel based morphometry: magnetic resonance histology
 2-2.5 months
Neuroreceptor levels: glutamate receptors: mGluR1
Increased
Description: mGluR5 levels are increased in the striatum in Shank3 null mice including in the postsynaptic density
Exp Paradigm: Western blot: striatum
 Western blot: striatum
 8 weeks
Hippocampal morphology1
Decreased
Description: Hippocampus is smaller in Shank3 null mice
 Voxel based morphometry: magnetic resonance histology
 2-2.5 months
Morphology of the basal ganglia: Lentiform nucleus: Globus pallidus1
Increased
Description: Volume of the globus pallidus (grey matter) is increased in Shank3 null mice
 Voxel based morphometry: magnetic resonance histology
 2-2.5 months
Thalamic morphology1
Increased
Description: Volume of the thalamus is increased in Shank3 null mice
 Voxel based morphometry: magnetic resonance histology
 2-2.5 months
Morphology and size of stria terminalis1
Decreased
Description: Strial terminalis white matter tracts are smaller in Shank3 null mice
 Voxel based morphometry: magnetic resonance histology
 2-2.5 months
Neuroreceptor levels: glutamate receptors: mGluR1
Increased
Description: mGluR5 levels are increased in the striatum in Shank3 null mice including in the postsynaptic density
Exp Paradigm:  Immunostaining
 Immunostaining
 8 weeks
DTI: Fractional anisotropy or Relative anisotropy in brain regions1
Decreased
Description: Areas exhibiting reduced FA include genu of the corpus callosum, vingulum, anterior commissure, fimbria, optic tract, nigrostriatal bundles, cerebral peduncles, cerebellum and brainstem
 Diffusion Tensor imaging (DTI): Diffusion Tensor imaging (DTI)
 2-2.5 months
Morphology of the amygdala1
Decreased
Description: The amygdala is smaller in Shank3 null mice
 Voxel based morphometry: magnetic resonance histology
 2-2.5 months
Post-synaptic density size1
Decreased
Description: Striatal MSNs have reduced PSD size (length and thickness) in Shank3 null mice
 Electron microscopy: striatal medium spiny neurons (MSNs)
 8 weeks
Morphology and size of fimbria1
Decreased
Description: Fimbria is smaller in Shank3 null mice
 Voxel based morphometry: magnetic resonance histology
 2-2.5 months
Neuroreceptor levels: glutamate receptors: AMPA receptors1
Decreased
Description: GluN2A levels are reduced in the hippocampus of Shank3 null mice
 Western blot: hippocampus
 8 weeks
Dendritic architecture: spine density1
Decreased
Description: Striatal MSNs have reduced spine density in Shank3 null mice, combined with reduced frequency of SEPSCs, authors suggest a loss in excitatory synapses
 Golgi-Cox staining: striatal medium spiny neurons
 8 weeks
Morphology and size of the optic tract1
Decreased
Description: Optic tract is smaller in Shank3 null mice
 Voxel based morphometry: magnetic resonance histology
 2-2.5 months
Olfactory bulb morphology1
Decreased
Description: Olfactory areas are smaller than controls in Shank3 null mice
 Voxel based morphometry: magnetic resonance histology
 2-2.5 months
Morphology and size of anterior commissure1
Decreased
Description: Anterior commissure is smaller in Shank3 null mice
 Voxel based morphometry: magnetic resonance histology
 2-2.5 months
Morphology of the basal ganglia: Striatum: Caudoputamen1
Increased
Description: Volume of the striatal caudate putamen is increased in Shank3 null mice
 Voxel based morphometry: magnetic resonance histology
 2-2.5 months
Action potential firing1
Decreased
Description: Shank3 null mice also displayed lower unit firing rates in Nac both before and after introduction of the social stimulus
 In vivo local field potential (LFP) recordings: nucleus accumben (Nac)
 3-4 months
Event related oscillations (EROs) in electroencephalography (EEG): coherence1
Decreased
Description: A smaller task-induced increase in coherence is observed in the limbic network of Shank3 null mice
 In vivo local field potential (LFP) recordings: limbic network
 3-4 months
Synaptic plasticity: striatal LTD1
Decreased
Description: Striatal LTD measured in the MSN synapses is reduced significantly in Shank3 null mice
 Whole-cell patch clamp: dorsostriatal medium spiny neurons
 2-5 months
Event related oscillations (EROs) in electroencephalography (EEG)1
Decreased
Description: Reduced oscillatory power is noted in the nucleus accumbens in the 7-11 Hz band of Shank3 null mice both before and after being exposed ot a social stimulus
 In vivo local field potential (LFP) recordings: after exposure to social stimulus
 3-4 months
Spontaneous post synaptic event frequency: excitatory currents1
Decreased
Description: SEPSC frequency is reduced in the striatal MSNs of Shank3 null mice
 Whole-cell patch clamp: striatal medium spiny neurons (MSNs)
 2-5 months
Action potential firing1
Increased
Description: Striatal MSNs have increased spikes in response to depolarizing steps of current in Shank3 null mice indicating a tendency for hyper-excitability
 Whole-cell patch clamp: striatal MSNs
 2-5 months
Presynaptic function1
Decreased
Description: After a HFS probability of presynaptic release did not increase significantly in Shank3 null mice, unlike controls where HFS causes an increase in the probability of release
 High-frequency stimulation (HFS)
 2-5 months
Self grooming: perseveration1
Increased
Description: Skin lesions were observed in greated than 50% Shank3 null mice caused by excessive self-grooming
 Grooming behavior assessments
 4-7 months
Startle response: acoustic stimulus1
Decreased
Description: Shank3 null mice have reduced acoustic startle reflex
 Acoustic startle reflex test
 Adult
Social dominance1
Decreased
Description: Dominance was not maintained across days in triads containing 3 unfamiliar Shank3 null adults, unlike in wild type triads where dominance ranking was established in a day and maintained till day 6
 Dominance hierarchy formation
 >2 months
Self grooming: social context1
Increased
Description: During reciprocal social interaction test Shank3 null mice showed more self-grooming than controls
 Grooming behavior assessments: reciprocal interaction
 >2 months
Social scent marking or recognition1
Decreased
Description: No preference towards own home nest versus a similar one is observed in Shank3 nulls, even if Shank3 null pups perform similar to controls when only one nest sample is provided
 Homing test
 P15
Ultrasonic vocalization: Interaction induced: opposite sex stimulus1
Decreased
Description: Adult male Shank3 null mice make fewer calls of shorter duration in response to female in estrus, compared to controls
 Monitoring ultrasonic vocalizations
 Adult
Ultrasonic vocalization: Isolation induced1
Decreased
Description: Shank3 null pups make fewer calls of decreased duration compared to control pups after being separated from mother
 Monitoring ultrasonic vocalizations
 P4
Developmental trajectory1
Decreased
Description: Shank3 null mice have some delays in achieving developmental milestones, like ear opening and paw positioning
 General observations
 P4
Anxiety1
Increased
Description: Shank3 null mice have increased latency to enter the lighted chamber than littermate and also try to escape from all new environments
 Light-dark exploration test: Light-dark exploration test
 Adult
Exploratory activity1
Decreased
Description: Shank3 null mice have a high tendency to escape from any new environment and do not show normal exploratory activity
Exp Paradigm: Home cage behavior
 Home cage behavior
 Adult
Exploratory activity1
Decreased
Description: Shank3 null mice have a high tendency to escape from any new environment and do not show normal exploratory activity
Exp Paradigm:  Novel cage test
 Novel cage test
 Adult
Reward reinforced choice behavior1
Decreased
Description: Shank3 null mice do not learn the task in which food pellet is 'earned' after lever-press in the 7 days of continuous reinforcement training, a striatal dependent task
 Operant conditioning paradigm: continuous reinforcement training
 Adult
Cognitive flexibility1
Decreased
Description: Shank3 null mice have significant impairment in the reversal phase of Morris water maze test compared to controls
 Morris water maze test: reversal training phase
 Adult
Spatial reference memory1
Decreased
Description: Shank3 null mice have impaired memory of the target quadrant in the probe trial
 Morris water maze test: probe trial and reversal phase probe trial
 Adult
Protein phosphorylation1
Increased
Description: Phosphorylated forms of Erk 1 and 2 (p-ERK 1/2)and S6K (p-S6K) are increased in Shank3 null mice
 Western blot: striatum
 8 weeks
Protein localization: synapse1
Decreased
Description: Homer2, Homer 1b/c are reduced in the striatal and hippocampal synapses while SAPAP and SAPAP3 are reduced in the synapses only in the striatal synapses of Shank3 null mice
 Western blot: striatum and hippocampus
 8 weeks
Mortality/lethality1
 No Change
 General observations
 Adult
Size/growth1
 No Change
 Body weight measurement
 P21, 3-6 months
Cued or contextual fear conditioning: Memory of context1
 No Change
 Fear conditioning test
 Adult
Cued or contextual fear conditioning: Memory of cue1
 No Change
 Fear conditioning test
 Adult
Olfactory learning and memory1
 No Change
 Olfactory habituation-dishabituation test
 2 months
Spatial learning1
 No Change
 Morris water maze test
 Adult
Gene expression1
 No Change
 Quantitative PCR (qRT-PCR): striatum and hippocampus
 8 weeks
Grip strength1
 No Change
 Grip strength test
 
Swimming ability1
 No Change
 Morris water maze test: visible platform phase
 Adult
Dendritic architecture: spine density1
 No Change
 Golgi-Cox staining: hippocampal neurons
 8 weeks
Morphology and size of fornix1
 No Change
 Voxel based morphometry: magnetic resonance histology
 2-2.5 months
Neuroreceptor levels: glutamate receptors: AMPA receptors1
 No Change
 Western blot: striatum
 8 weeks
Post-synaptic density size1
 No Change
 Electron microscopy: hippocampal neurons
 8 weeks
Intrinsic membrane properties1
 No Change
 Whole-cell patch clamp: striatal medium spiny neurons (MSNs)
 2-5 months
Spontaneous post synaptic event amplitude: excitatory currents1
 No Change
 Whole-cell patch clamp: striatal medium spiny neurons (MSNs)
 2-5 months
Repetitive nose pokes1
 No Change
 Hole-board test
 4-7 months
Seizures1
 No Change
 Observation of seizures
 Adult
Sensorimotor gating1
 No Change
 Prepulse inhibition
 Adult
Vision1
 No Change
 Morris water maze test: visible platform phase
 Adult
Social approach1
 No Change
 Three-chamber social approach test
 >2 months
Social interaction1
 No Change
 Reciprocal social interaction test
 >2 months
 Not Reported: Circadian sleep/wake cycle, Homeostasis, Immune response, Maternal behavior

M_SHANK3_19_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Ultrasonic vocalization: Isolation induced1
 No Change
 Monitoring ultrasonic vocalizations
 P4
Anxiety1
 No Change
 Light-dark exploration test: Light-dark exploration test
 Adult
Cognitive flexibility1
 No Change
 Morris water maze test: probe trial and reversal phase probe trial
 Adult
Olfactory learning and memory1
 No Change
 Olfactory habituation-dishabituation test
 Adult
Spatial learning1
 No Change
 Morris water maze test
 Adult
Spatial reference memory1
 No Change
 Morris water maze test: probe trial and reversal phase probe trial
 8 weeks
Protein localization: synapse1
 No Change
 Western blot
 Adult
General locomotor activity1
 No Change
 Open field test
 Adult
Grip strength1
 No Change
 Grip strength test
 Adult
Neuroreceptor levels: glutamate receptors: AMPA receptors1
 No Change
 Western blot: hippocampus
 8 weeks
Repetitive nose pokes1
 No Change
 Hole-board test
 Adult
Sensorimotor gating1
 No Change
 Prepulse inhibition
 Adult
Vision1
 No Change
 Morris water maze test: visible platform phase
 Adult
Social approach1
 No Change
 Three-chamber social approach test
 Adult
Social interaction1
 No Change
 Reciprocal social interaction test
 Adult
Social memory1
 No Change
 Three-chamber social approach test
 Adult
Social scent marking or recognition1
 No Change
 Homing test
 Adult
 Not Reported: Circadian sleep/wake cycle, Developmental profile, Homeostasis, Immune response, Maternal behavior, Neurophysiology, Seizure

M_SHANK3_20_CKO_HM_NAc

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Action potential firing1
Decreased
Description: Striatal MSNs have significantly reduced spiking frequency in mutants with Shank3 knocked out in the Nac, compared to controls, indicating that the loss of Shank3 locally and specifically in the NAc causes the reduction in spiking, similar to what is observed in the complete KO
 In vivo local field potential (LFP) recordings: nucleus accumben (Nac)
 3-4 months
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / Ultrastructure / Cytoarchitecture, Repetitive behavior, Seizure, Sensory, Social behavior

M_SHANK3_4_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Touch1
Increased
Description: Shank3 hets show an increased response to just air puff indicating aberrant sensitivity or hypersensitivity
 Response to air puff
 6-8 weeks
Tactile discrimination and memory1
Decreased
Description: Shank3 hets have reduced discrimination and memory for objects differing in texture (rough or smooth) and do not preferentially interact with a novel textured-object over a familiar one
 Textured novel object recognition test (T-NORT)
 6-8 weeks
Sensorimotor gating: tactile cue1
Decreased
Description: Tactile prepulse inhibition responses are enhanced in Shank3 het mice, as opposed to control littermates that display reduced magnitude of acoustic startle response when they receive an air puff prepulse
 Prepulse inhibition: air puff stimulus
 6-8 weeks
Social approach2
Decreased
Description: Mutants show reduced preference for an unfamiliar mouse in comparison to an empty cup compared with controls.
 Three-chamber social approach test
 7-10 weeks
Object recognition memory: long-term recall1
Decreased
Description: Shank3 het mice have reduced preference for novel object when the retention period (or interval) is extended to 1 hr from 5 min, whereas WT mice still prefer the novel object
 Novel object recognition test
 6-8 weeks
Exploratory activity1
 No Change
 Textured novel object recognition test (T-NORT)
 6-8 weeks
Object recognition memory1
 No Change
 Novel object recognition test
 6-8 weeks
Sensorimotor gating1
 No Change
 Prepulse inhibition
 6-8 weeks
Startle response: acoustic stimulus1
 No Change
 Acoustic startle reflex test
 6-8 weeks
Social memory2
 No Change
 Three-chamber social approach test
 7-10 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / Ultrastructure / Cytoarchitecture, Neurophysiology, Repetitive behavior, Seizure, Sensory, Social behavior

M_SHANK3_23_KI_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Motor coordination and balance1
Decreased
Description: Shank3 KO females have decreased latency to fall off the accelerating rotarod as control females
 Accelerating rotarod test
 5.4- 9 weeks
Synaptic plasticity: hippocampal LTP1
Decreased
Description: Shank3 mutants have reduced NMDAR mediated LTP in the CA1-Schaffer collateral synapses
 Whole-cell patch clamp
 4-6 weeks
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission1
Decreased
Description: Shank3 KOs have reduced ratio NMDAR/AMPAR mediated current in medium spiny neurons of the dorsal striatum
 Whole-cell patch clamp
 4-6 weeks
Repetitive digging1
Decreased
Description: Shank3 KO mice bury fewer marbles compared to controls
 Marble-burying test
 5.4- 9 weeks
Self grooming: perseveration1
Increased
Description: Shank3 KO's spend significantly more time in self-grooming compared to controls
 Grooming behavior assessments
 5.4- 9 weeks
Social interaction1
Decreased
Description: Shank3 KO's spend significantly less time interacting with a caged mouse
 Partition test
 5.4- 9 weeks
Social interaction1
Decreased
Description: Shank3 KO's spend reduced amount of time and number of bouts interacting with sex, age and genotyped matched mouse
 Reciprocal social interaction test
 5.4- 9 weeks
Social memory: long-term social memory1
Decreased
Description: Shank3 KO's have reduced social recognition memory as do not show a decrease in interaction time with a familiar juvenile mouse
 Social recognition test
 5.4- 9 weeks
Social memory1
Decreased
Description: Shank3 KO's have no preference for novel target mouse compared to familiar mouse
 Three-chamber social approach test
 5.4- 9 weeks
Exploratory activity1
Decreased
Description: Shank3 KO male and female mice show decreased rearing behavior, authors note this as a sign of exploratory behavior
 Home cage behavior
 5.4- 9 weeks
Thigmotaxis1
Increased
Description: Shank3 KOs display increased thigmotaxis and poor transition to improved spatial strategy compared to controls
 Morris water maze test
 5.4- 9 weeks
Spatial reference memory1
Decreased
Description: Shank3 KOs have impaired spatial reference memory and show no preference to the target quadrant
 Morris water maze test
 5.4- 9 weeks
Spatial learning1
Decreased
Description: Shank3 KO mice have impaired spatial learning as they show significantly increased latency to find the hidden platform
 Morris water maze test
 5.4- 9 weeks
Protein expression level evidence1
Decreased
Description: Homer 1b/c is decreased in striatal synaptosomal fraction from Shank3 KO mice
 Western blot
 4 weeks
Targeted expression1
Decreased
Description: Shank3 KO mice have loss of expression of higher molecular weight Shank3 isoforms
 Western blot
 4 weeks
Protein expression level evidence1
Decreased
Description: GluN1 is reduced in Shank3 KO whole brain lysate
 Western blot
 4 weeks
Protein expression level evidence1
Decreased
Description: PSD-95 is decreased in striatal synaptosomal fraction from Shank3 KO mice
 Western blot
 4 weeks
Protein expression level evidence1
Decreased
Description: GluA3 (Glu-R3) is decreased in striatal synaptosomal fraction from Shank3 KO mice
 Western blot
 4 weeks
Protein expression level evidence1
Decreased
Description: Homer 1b/c is reduced in Shank3 KO whole brain lysate
 Western blot
 4 weeks
Protein expression level evidence1
Decreased
Description: GluA2 (GluR-2) is decreased in striatal synaptosomal fraction from Shank3 KO mice
 Western blot
 4 weeks
Anxiety1
 No Change
 Light-dark exploration test: Light-dark exploration test
 5.4- 9 weeks
Anxiety1
 No Change
 Elevated plus maze test
 5.4- 9 weeks
Anxiety1
 No Change
 Open field test
 5.4- 9 weeks
General locomotor activity1
 No Change
 Open field test
 5.4- 9 weeks
General locomotor activity: Ambulatory activity1
 No Change
 Open field test
 5.4- 9 weeks
Motor coordination and balance1
 No Change
 Accelerating rotarod test
 5.4- 9 weeks
EPSP-spike relationship1
 No Change
 Field potential recordings
 4-6 weeks
Presynaptic function: paired-pulse depression (PPD)1
 No Change
 Paired-pulse ratio
 4-6 weeks
Synaptic plasticity: hippocampal LTD1
 No Change
 Whole-cell patch clamp
 4-6 weeks
Synaptic transmission1
 No Change
 Field potential recordings
 4-6 weeks
Sensorimotor gating1
 No Change
 Prepulse inhibition
 5.4- 9 weeks
Startle response: acoustic stimulus1
 No Change
 Acoustic startle reflex test
 5.4- 9 weeks
Social approach1
 No Change
 Three-chamber social approach test
 5.4- 9 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Homeostasis, Immune response, Maternal behavior, Neuroanatomy / Ultrastructure / Cytoarchitecture, Seizure

M_SHANK3_23_KI_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Motor coordination and balance1
Increased
Description: Shank3 het males have increased latency to fall off the accelerating rotarod compared to controls
 Accelerating rotarod test
 5.4- 9 weeks
Synaptic plasticity: hippocampal LTP1
Decreased
Description: Shank3 mutants have reduced NMDAR mediated LTP in the CA1-Schaffer collateral synapses
 Whole-cell patch clamp
 4-6 weeks
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission1
Decreased
Description: Shank3 hets have reduced ratio NMDAR/AMPAR mediated current in medium spiny neurons of the dorsal striatum
 Whole-cell patch clamp
 4-6 weeks
Self grooming: perseveration1
Increased
Description: Shank3 hets spend significantly more time in self-grooming compared to controls
 Grooming behavior assessments
 5.4- 9 weeks
Social memory: long-term social memory1
Decreased
Description: Shank3 hets have reduced social recognition memory as do not show a decrease in interaction time with a familiar juvenile mouse
 Social recognition test
 5.4- 9 weeks
Social memory1
Decreased
Description: Shank3 hets have no preference for novel target mouse compared to familiar mouse
 Three-chamber social approach test
 5.4- 9 weeks
Social approach1
Decreased
Description: Shank3 hets show no preference for social target vs empty cage
 Three-chamber social approach test
 5.4- 9 weeks
Exploratory activity1
Decreased
Description: Shank3 het females show decreased rearing behavior in their home cage, authors note this as a sign of exploratory behavior
 Home cage behavior
 5.4- 9 weeks
Protein expression level evidence1
Decreased
Description: GluN2B is decreased in striatal synaptosomal fraction from Shank3 hets
 Western blot
 4 weeks
Targeted expression1
Decreased
Description: Shank3 hets have resuced expression of higher mol wt isoforms of Shank3
 Western blot
 4 weeks
Protein expression level evidence1
Decreased
Description: GluN1is decreased in hippocampal synaptosomal fraction from Shank3 hets
 Western blot
 4 weeks
Protein expression level evidence1
Decreased
Description: PSD-95 is decreased in striatal synaptosomal fraction from Shank3 hets
 Western blot
 4 weeks
Protein expression level evidence1
Decreased
Description: GluA1 (GluR-1) is decreased in hippocampal synaptosomal fraction from Shank3 hets
 Western blot
 4 weeks
Protein expression level evidence1
Decreased
Description: Homer 1b/c is decreased in striatal synaptosomal fraction from Shank3 hets
 Western blot
 4 weeks
Anxiety1
 No Change
 Light-dark exploration test: Light-dark exploration test
 5.4- 9 weeks
Exploratory activity1
 No Change
 Home cage behavior
 5.4- 9 weeks
Thigmotaxis1
 No Change
 Morris water maze test
 5.4- 9 weeks
Spatial learning1
 No Change
 Morris water maze test
 5.4- 9 weeks
Spatial reference memory1
 No Change
 Morris water maze test
 5.4- 9 weeks
General locomotor activity1
 No Change
 Open field test
 5.4- 9 weeks
Motor coordination and balance1
 No Change
 Accelerating rotarod test
 5.4- 9 weeks
Repetitive digging1
 No Change
 Marble-burying test
 5.4- 9 weeks
Social interaction1
 No Change
 Reciprocal social interaction test
 5.4- 9 weeks
Social interaction1
 No Change
 Partition test
 5.4- 9 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Homeostasis, Immune response, Maternal behavior, Neuroanatomy / Ultrastructure / Cytoarchitecture, Seizure, Sensory

M_SHANK3_4_KO_HM_L-reuteri

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Neuroreceptor levels: GABA-R: GABAA1
Ameliorated
Description: Male Shank3 mutant mice treated with L. reuteri show a robust increase in the hippocampal expression of GABRA2 and GABRB1, and a modest decrease in hippocampal GABRA1, compared to untreated mutants. Male Shank3 mutant mice treated with L. reuteri show increase in GABRA2, GABRB1, and GABRA1, compared to untreated mutants, in the prefrontal cortex. Female Shank3 mutant mice treated with L. reuteri show an increase in GABRA1, GABRA2, and GABRB1 gene expression in the hippocampus, and an in increase in GABRA1 and GABRA2 expression in the prefrontal cortex compared to untreated mutants. Wildtype male mice treated with L. reuteri show no changes in GABA receptor gene expression levels in the hippocampus compared to untreated controls.
 Quantitative PCR (qRT-PCR)
 3 months
Neuroreceptor levels: GABA-R: GABAA1
Ameliorated
Description: Shank3 mutants treated with L. reuteri show increased in GABRA1 protein levels in the frontal cortex in males and females, and an increase in the hippocampus in female mutants, compared to untreated controls.
 Western blot
 3 months
Repetitive digging1
Ameliorated
Description: Shank3 mutants treated with L. reuteri buried fewer marbles than untreated mutants. Wildtype mice treated with L.reuteri show no change in marble burying.
 Marble-burying test
 3 months
Social approach1
Refractory
Description: Female Shank3 mutant mice treated with L. reuteri showed no change in preference for empty and occupied compartments compared to untreated mutants. L.reuteri treatment on wildtype mice showed no change in social behaviors.
 Three-chamber social approach test
 3 months
Social approach1
Ameliorated
Description: Male Shank3 mutants treated with L. reuteri showed no preference for the empty or occupied chamber compared to untreated mutants that showed preference for the empty chamber. Male shank3 mutants treated with L. reuteri spent more time investigating the compartment with the unfamiliar mouse compared to untreated mutants. L.reuteri treatment on wildtype mice showed no change in social behaviors.
 Three-chamber social approach test
 3 months
Anxiety1
Refractory
Description: Shank3 mutants treated with L. reuteri spent more time in the center of the open field compared to untreated mutants. Wildtype mice treated with L. reuteri show no change in anxiety.
 Open field test
 3 months
Anxiety1
Refractory
Description: Shank3 mutants treated with L. reuteri spent more time in the open arms of the elevated plus maze compared to untreated mutants. Wildtype mice treated with L. reuteri show no change in anxiety.
 Elevated plus maze test
 3 months
Cytokine levels: pro-inflammatory1
Refractory
Description: Shank3 mutant mice treated with L. reuteri show no change in the levels of IL-17a compared to untreated mutants.
 ELISA
 3 months
Cytokine levels: anti-inflammatory1
Restored
Description: Shank3 mutant mice treated with L. reuteri show normal levels of IL-10 compared to untreated mutants.
 ELISA
 3 months
Cytokine levels: pro-inflammatory1
Restored
Description: Shank3 mutant mice treated with L. reuteri show normal levels of IL-1b, TNF-alpha, IFN-gamma and IL-6, compared to untreated mutants.
 ELISA
 3 months
Gene expression1
Ameliorated
Description: Male shank3 mutants treated with L. reuteri show increased expression of oxytocin gene in the hypothalamus compared to untreated controls.
 Quantitative PCR (qRT-PCR): oxytocin
 3 months
Gene expression1
Refractory
Description: Female shank3 mutants treated with L. reuteri show decreased expression of oxytocin gene in the hypothalamus compared to untreated controls.
 Quantitative PCR (qRT-PCR): oxytocin
 3 months
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Homeostasis, Learning & memory, Maternal behavior, Motor phenotype, Neurophysiology, Seizure, Sensory

M_Shank3_24_KD

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Object recognition memory1
Decreased
Description: Shank3-siRNA injected mice show decrease in time spent with an unfamiliar object over a familiar object compared with controls.
 Object preference test
 Adult
Targeted expression1
Decreased
Description: Shank3-siRNA injected mice show decrease in Shank3 transcript in the dorsal striatum, 2 days after injection.
Exp Paradigm: Striatal tissue was used for qRT PCR.
 Quantitative PCR (qRT-PCR)
 Adult
Repetitive digging1
 No Change
 Home cage behavior
 Adult
Self grooming: perseveration1
 No Change
 Grooming behavior assessments
 Adult
Social memory1
 No Change
 U-field assay
 Adult
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Maternal behavior, Motor phenotype, Neuroanatomy / Ultrastructure / Cytoarchitecture, Neurophysiology, Seizure, Sensory


Interactor Symbol Interactor Name Interactor Organism Entrez ID Uniprot ID Interaction Type Evidence Reference
ABI2 abl-interactor 2 10152 Q9NYB9 Y2H
Sakai Y , et al. 2011
ACTN1 actinin, alpha 1 87 P12814 Y2H; IP/WB; GST
Sakai Y , et al. 2011
ACTN2 actinin, alpha 2 88 P35609 Y2H
Sakai Y , et al. 2011
AGAP7 ArfGAP with GTPase domain, ankyrin repeat and PH domain 7 653268 Q5VUJ5 Y2H
Sakai Y , et al. 2011
ALDOA aldolase A, fructose-bisphosphate 226 P04075 Y2H
Sakai Y , et al. 2011
ANKRD35 ankyrin repeat domain 35 148741 Q8N283 Y2H
Sakai Y , et al. 2011
APP amyloid beta (A4) precursor protein 351 P05067 Y2H
Sakai Y , et al. 2011
ARPC2 actin related protein 2/3 complex, subunit 2, 34kDa 10109 O15144 Y2H
Sakai Y , et al. 2011
ARPC5L actin related protein 2/3 complex, subunit 5-like 81873 Q9BPX5 Y2H
Sakai Y , et al. 2011
ATN1 atrophin 1 1822 P54259 Y2H
Sakai Y , et al. 2011
C1QBP complement component 1, q subcomponent binding protein 708 Q07021 Y2H
Sakai Y , et al. 2011
C6orf154 chromosome 6 open reading frame 154 221424 Q5JTD7 Y2H
Sakai Y , et al. 2011
CA10 carbonic anhydrase X 56934 Q9NS85 Y2H
Sakai Y , et al. 2011
CALCOCO1 calcium binding and coiled-coil domain 1 57658 Q9P1Z2 Y2H
Sakai Y , et al. 2011
CAMK2B calcium/calmodulin-dependent protein kinase II beta 816 Q13554 Y2H
Sakai Y , et al. 2011
CCT3 chaperonin containing TCP1, subunit 3 (gamma) 7203 P49368 Y2H
Sakai Y , et al. 2011
CENPJ centromere protein J 55835 Q9HC77 Y2H
Sakai Y , et al. 2011
CEP72 centrosomal protein 72kDa 55722 Q9P209 Y2H
Sakai Y , et al. 2011
CLTA clathrin, light chain A 1211 P09496 Y2H
Sakai Y , et al. 2011
CLU clusterin 1191 P10909 Y2H
Sakai Y , et al. 2011
COPS6 COP9 constitutive photomorphogenic homolog subunit 6 (Arabidopsis) 10980 Q7L5N1 Y2H
Sakai Y , et al. 2011
COQ5 coenzyme Q5 homolog, methyltransferase (S. cerevisiae) 84274 Q5HYK3 Y2H
Sakai Y , et al. 2011
CRELD1 cysteine-rich with EGF-like domains 1 78987 Q96HD1 Y2H
Sakai Y , et al. 2011
CSNK1D casein kinase 1, delta 1453 P48730 Y2H
Sakai Y , et al. 2011
CTNND2 catenin (cadherin-associated protein), delta 2 1501 Q9UQB3 IP/WB
Quitsch A , et al. 2005
CYP51A1 cytochrome P450, family 51, subfamily A, polypeptide 1 1595 Q16850 Y2H
Sakai Y , et al. 2011
CYTIP cytohesin 1 interacting protein 9595 O60759 Y2H
Sakai Y , et al. 2011
DCTN2 dynactin 2 (p50) 10540 Q13561 Y2H
Sakai Y , et al. 2011
DDB1 damage-specific DNA binding protein 1, 127kDa 1642 Q16531 Y2H
Sakai Y , et al. 2011
DNAJA3 DnaJ (Hsp40) homolog, subfamily A, member 3 9093 Q96EY1 Y2H
Sakai Y , et al. 2011
DNM2 dynamin 2 1785 P50570 Y2H
Sakai Y , et al. 2011
EFEMP1 EGF containing fibulin-like extracellular matrix protein 1 2202 Q12805 Y2H
Sakai Y , et al. 2011
EFEMP2 EGF containing fibulin-like extracellular matrix protein 2 30008 O95967 Y2H
Sakai Y , et al. 2011
EID1 EP300 interacting inhibitor of differentiation 1 23741 Q9Y6B2 Y2H
Sakai Y , et al. 2011
ELAVL1 ELAV (embryonic lethal, abnormal vision, Drosophila)-like 1 (Hu antigen R) 1994 Q15717 Y2H
Sakai Y , et al. 2011
ERI3 ERI1 exoribonuclease family member 3 79033 O43414 Y2H
Sakai Y , et al. 2011
FAM13A family with sequence similarity 13, member A 10144 O94988 Y2H
Sakai Y , et al. 2011
FAM92A1 family with sequence similarity 92, member A1 137392 A1XBS5 Y2H
Sakai Y , et al. 2011
FBXO7 F-box protein 7 25793 Q9Y3I1 Y2H
Sakai Y , et al. 2011
FKBP8 FK506 binding protein 8, 38kDa 23770 Q14318 Y2H
Sakai Y , et al. 2011
FLNA filamin A, alpha 2316 P21333 Y2H; IP/WB; GST
Sakai Y , et al. 2011
FRS3 fibroblast growth factor receptor substrate 3 10817 O43559 Y2H
Sakai Y , et al. 2011
FRYL FRY-like 285527 O94915 Y2H
Sakai Y , et al. 2011
GAPDH glyceraldehyde-3-phosphate dehydrogenase 2597 P04406 Y2H
Sakai Y , et al. 2011
GOT1 glutamic-oxaloacetic transaminase 1, soluble (aspartate aminotransferase 1) 2805 P17174 Y2H
Sakai Y , et al. 2011
GPR162 G protein-coupled receptor 162 27239 Q16538 Y2H
Sakai Y , et al. 2011
GPS1 G protein pathway suppressor 1 2873 Q13098 Y2H
Sakai Y , et al. 2011
GRN granulin 2896 P28799 Y2H
Sakai Y , et al. 2011
HAGH hydroxyacylglutathione hydrolase 3029 Q16775 Y2H
Sakai Y , et al. 2011
HCN1 hyperpolarization activated cyclic nucleotide-gated potassium channel 1 348980 O60741 IP/WB
Yi F , et al. 2016
HCN2 hyperpolarization activated cyclic nucleotide-gated potassium channel 2 610 Q9UL51 IP/WB
Yi F , et al. 2016
HCN3 hyperpolarization activated cyclic nucleotide gated potassium channel 3 57657 Q9P1Z3 IP/WB
Yi F , et al. 2016
HECW1 HECT, C2 and WW domain containing E3 ubiquitin protein ligase 1 23072 Q76N89 Y2H
Sakai Y , et al. 2011
HGS hepatocyte growth factor-regulated tyrosine kinase substrate 9146 O14964 Y2H
Sakai Y , et al. 2011
HNRNPC heterogeneous nuclear ribonucleoprotein C (C1/C2) 3183 P07910 Y2H; GST
Sakai Y , et al. 2011
HNRNPK heterogeneous nuclear ribonucleoprotein K 3190 P61978 Y2H
Sakai Y , et al. 2011
ICA1 islet cell autoantigen 1, 69kDa 3382 Q05084 Y2H
Sakai Y , et al. 2011
IGSF9 immunoglobulin superfamily, member 9 57549 Q9P2J2 Y2H
Sakai Y , et al. 2011
ITGBL1 integrin, beta-like 1 (with EGF-like repeat domains) 9358 O95965 Y2H
Sakai Y , et al. 2011
ITSN1 intersectin 1 (SH3 domain protein) 6453 Q15811 Y2H
Sakai Y , et al. 2011
JAG2 jagged 2 3714 Q9Y219 Y2H
Sakai Y , et al. 2011
KHDRBS1 KH domain containing, RNA binding, signal transduction associated 1 10657 Q07666 Y2H
Sakai Y , et al. 2011
KHDRBS3 KH domain containing, RNA binding, signal transduction associated 3 10656 O75525 Y2H; GST
Sakai Y , et al. 2011
KIAA0232 KIAA0232 9778 Q92628 Y2H
Sakai Y , et al. 2011
LINGO1 leucine rich repeat and Ig domain containing 1 84894 Q96FE5 Y2H
Sakai Y , et al. 2011
LOC727948 LOC727948similar to KIAA0454 protein 727948 N/A Y2H
Sakai Y , et al. 2011
LPHN1 latrophilin 1 22859 O94910 Y2H
Sakai Y , et al. 2011
LRRC7 leucine rich repeat containing 7 57554 Q96NW7 IP/WB
Quitsch A , et al. 2005
LTBP3 latent transforming growth factor beta binding protein 3 4054 Q9NS15 Y2H
Sakai Y , et al. 2011
LTBP4 latent transforming growth factor beta binding protein 4 8425 Q8N2S1 Y2H
Sakai Y , et al. 2011
MBIP MAP3K12 binding inhibitory protein 1 51562 Q9NS73 Y2H
Sakai Y , et al. 2011
MBOAT7 membrane bound O-acyltransferase domain containing 7 79143 Q96N66 Y2H
Sakai Y , et al. 2011
MCRS1 microspherule protein 1 10445 Q96EZ8 Y2H
Sakai Y , et al. 2011
MDH2 malate dehydrogenase 2, NAD (mitochondrial) 4191 P40926 Y2H
Sakai Y , et al. 2011
MEGF10 multiple EGF-like-domains 10 84466 Q96KG7 Y2H
Sakai Y , et al. 2011
MEGF11 multiple EGF-like-domains 11 84465 A6BM72 Y2H
Sakai Y , et al. 2011
MEGF6 multiple EGF-like-domains 6 1953 O75095 Y2H
Sakai Y , et al. 2011
MIPOL1 mirror-image polydactyly 1 145282 Q8TD10 Y2H
Sakai Y , et al. 2011
MT-CO2 Cytochrome c oxidase subunit 2 4513 P00403 Y2H
Sakai Y , et al. 2011
MT-ND6 mitochondrially encoded NADH dehydrogenase 6 4541 P03923 Y2H
Sakai Y , et al. 2011
MYO5B myosin VB 4645 Q9ULV0 Y2H
Sakai Y , et al. 2011
N4BP3 NEDD4 binding protein 3 23138 O15049 Y2H
Sakai Y , et al. 2011
NCKIPSD NCK interacting protein with SH3 domain 51517 Q9NZQ3 Y2H
Sakai Y , et al. 2011
NEFL neurofilament, light polypeptide 4747 P07196 Y2H
Sakai Y , et al. 2011
NELL2 NEL-like 2 (chicken) 4753 Q99435 Y2H; GST
Sakai Y , et al. 2011
NGRN neugrin, neurite outgrowth associated 51335 Q9NPE2 Y2H
Sakai Y , et al. 2011
NOTCH1 notch 1 4851 P46531 Y2H
Sakai Y , et al. 2011
NOTCH2 notch 2 4853 Q04721 Y2H
Sakai Y , et al. 2011
NOTCH2NL notch 2 N-terminal like 388677 Q7Z3S9 Y2H
Sakai Y , et al. 2011
NOTCH3 notch 3 4854 Q9UM47 Y2H
Sakai Y , et al. 2011
NR1D1 nuclear receptor subfamily 1, group D, member 1 9572 P20393 Y2H
Sakai Y , et al. 2011
NRBF2 nuclear receptor binding factor 2 29982 Q96F24 Y2H
Sakai Y , et al. 2011
PDHB pyruvate dehydrogenase (lipoamide) beta 5162 P11177 Y2H
Sakai Y , et al. 2011
PFKL phosphofructokinase, liver 5211 P17858 Y2H
Sakai Y , et al. 2011
PHF12 PHD finger protein 12 57649 Q96QT6 Y2H
Sakai Y , et al. 2011
PHLDB1 pleckstrin homology-like domain, family B, member 1 23187 Q86UU1 Y2H
Sakai Y , et al. 2011
PICK1 protein interacting with PRKCA 1 9463 Q9NRD5 Y2H; GST
Sakai Y , et al. 2011
PLEKHA4 pleckstrin homology domain containing, family A (phosphoinositide binding specific) member 4 57664 Q9H4M7 Y2H
Sakai Y , et al. 2011
PPHLN1 periphilin 1 51535 Q8NEY8 Y2H
Sakai Y , et al. 2011
PPP1R13L protein phosphatase 1, regulatory (inhibitor) subunit 13 like 10848 Q8WUF5 Y2H
Sakai Y , et al. 2011
PPP1R9B protein phosphatase 1, regulatory (inhibitor) subunit 9B 84687 Q96SB3 Y2H
Sakai Y , et al. 2011
PPP2R3B protein phosphatase 2, regulatory subunit B'', beta 28227 Q9Y5P8 Y2H
Sakai Y , et al. 2011
PRMT2 protein arginine methyltransferase 2 3275 P55345 Y2H
Sakai Y , et al. 2011
PRMT2 protein arginine methyltransferase 2 3275 P55345 IP; LC-MS/MS
Huttlin EL , et al. 2015
PSMD4 proteasome (prosome, macropain) 26S subunit, non-ATPase, 4 5710 P55036 Y2H; GST
Sakai Y , et al. 2011
QSOX1 quiescin Q6 sulfhydryl oxidase 1 5768 O00391 Y2H
Sakai Y , et al. 2011
RBM5 RNA binding motif protein 5 10181 P52756 Y2H
Sakai Y , et al. 2011
Ret ret proto-oncogene 19713 P35546 Y2H; IP/WB
Schuetz G , et al. 2004
RICH2 Rho GTPase-activating protein 44 9912 Q17R89 Y2H
Sakai Y , et al. 2011
RNMTL1 RNA methyltransferase like 1 55178 Q9HC36 Y2H
Sakai Y , et al. 2011
RPL3 ribosomal protein L3 6122 P39023 Y2H
Sakai Y , et al. 2011
RTN3 reticulon 3 10313 O95197 Y2H
Sakai Y , et al. 2011
RUNDC3A RUN domain containing 3A 10900 Q59EK9 Y2H
Sakai Y , et al. 2011
SCYL3 SCY1-like 3 (S. cerevisiae) 57147 Q8IZE3 Y2H
Sakai Y , et al. 2011
SETD2 SET domain containing 2 29072 Q9BYW2 Y2H
Sakai Y , et al. 2011
SFRS9 serine/arginine-rich splicing factor 9 8683 Q13242 Y2H
Sakai Y , et al. 2011
SH3GL2 SH3-domain GRB2-like 2 6456 Q99962 Y2H
Sakai Y , et al. 2011
SH3GL3 SH3-domain GRB2-like 3 6457 Q99963 Y2H
Sakai Y , et al. 2011
SHANK1 SH3 and multiple ankyrin repeat domains 1 50944 Q9Y566 Y2H; IP/WB
Sakai Y , et al. 2011
SHARPIN SHANK-associated RH domain interactor 81858 Q9H0F6