HELP     Sign In
Search

Relevance to Autism

Several studies have identified rare mutations in the SHANK2 gene in autistic and intellectually disabled individuals (Berkel et al., 2010; Pinto et al., 2010; Leblond et al., 2012; Sanders et al., 2012). A functional study analyzed three of the mutations previously found in individuals with ASD (L1008_P1009dup, T1127M and R462X). The mutations were found to have varying effects on protein localization, dendritic spine volume and branching in cultured neurons and even synaptic transmission and cognitive behavior in mice, with the R462X variant causing the most severe phenotypes (Berkel et al., 2012).

Molecular Function

Shank proteins contain multiple domains for protein-protein interactions and function as molecular scaffolds in the postsynaptic density (PSD).

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Mutations in the SHANK2 synaptic scaffolding gene in autism spectrum disorder and mental retardation.
ASD
MR
Positive Association
Genetic association between SHANK2 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
Support
Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study.
ID
Epilepsy, ASD
Support
Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.
ASD
Support
Whole genome sequencing and variant discovery in the ASPIRE autism spectrum disorder cohort.
ASD
Support
De novo mutations revealed by whole-exome sequencing are strongly associated with autism.
ASD
Support
Genome-wide characteristics of de novo mutations in autism.
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
Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders.
ASD
ID
Support
Whole-genome sequencing in multiplex families with psychoses reveals mutations in the SHANK2 and SMARCA1 genes segregating with illness.
SCZ
Support
Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
ASD
Support
Functional impact of global rare copy number variation in autism spectrum disorders.
ASD
Support
Dysfunction of SHANK2 and CHRNA7 in a patient with intellectual disability and language impairment supports genetic epistasis of the two loci.
DD, ID
Support
Eighteen-year-old man with autism, obsessive compulsive disorder and a SHANK2 variant presents with severe anorexia that responds to high-dose fluo...
ASD, OCD
Support
Breakpoint mapping by next generation sequencing reveals causative gene disruption in patients carrying apparently balanced chromosome rearrangemen...
DD, ID
Autistic behavior
Support
A direct regulatory link between microRNA-137 and SHANK2: implications for neuropsychiatric disorders.
Support
A discovery resource of rare copy number variations in individuals with autism spectrum disorder.
ASD
Support
Genomic diagnosis for children with intellectual disability and/or developmental delay.
ID, ADHD
Highly Cited
Proline-rich synapse-associated proteins ProSAP1 and ProSAP2 interact with synaptic proteins of the SAPAP/GKAP family.
Highly Cited
The interaction of phospholipase C-beta3 with Shank2 regulates mGluR-mediated calcium signal.
Highly Cited
The Shank family of scaffold proteins.
Recent Recommendation
Inherited and de novo SHANK2 variants associated with autism spectrum disorder impair neuronal morphogenesis and physiology.
ASD
ID
Recent Recommendation
SHANK2 mutations associated with autism spectrum disorder cause hyperconnectivity of human neurons.
ASD
Recent Recommendation
Activity induced changes in the distribution of Shanks at hippocampal synapses.
Recent Recommendation
Effect of the autism-associated lncRNA Shank2-AS on architecture and growth of neurons.
Recent Recommendation
BetaPix up-regulates Na? exchanger 3 through a Shank2-mediated protein-protein interaction.
Recent Recommendation
Low load for disruptive mutations in autism genes and their biased transmission.
ASD
Recent Recommendation
AnkyrinG is required to maintain axo-dendritic polarity in vivo.
Recent Recommendation
Identification and functional characterization of rare SHANK2 variants in schizophrenia.
SCZ
Recent Recommendation
Integrated systems analysis reveals a molecular network underlying autism spectrum disorders.
ASD
Recent Recommendation
Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: a gradient of severity in cognitive impairments.
ASD

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN229R001 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN229R002 
 stop_gained 
 c.1384C>T 
 p.Arg462Ter 
 De novo 
  
 Simplex 
 GEN229R003 
 missense_variant 
 c.76C>T 
 p.Arg26Trp 
 Familial 
 Paternal 
  
 GEN229R004 
 missense_variant 
 c.622C>T 
 p.Pro208Ser 
 Familial 
 Maternal 
 Multiplex 
 GEN229R005 
 inframe_insertion 
 c.3024_3029dup 
 p.Leu1008_Pro1009dup2 
 Familial 
 Maternal 
  
 GEN229R006 
 missense_variant 
 c.3380C>T 
 p.Thr1127Met 
 Familial 
 Maternal 
  
 GEN229R007 
 missense_variant 
 c.4048G>A 
 p.Ala1350Thr 
 Familial 
 Maternal 
 Multiplex 
 GEN229R008 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN229R009 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN229R010 
 copy_number_loss 
  
  
 De novo 
  
  
 GEN229R011 
 missense_variant 
 c.1327C>T 
 p.Arg443Cys 
  
  
  
 GEN229R012 
 missense_variant 
 C>A 
 p.Arg598Leu 
  
  
  
 GEN229R013 
 missense_variant 
 c.2149G>T 
 p.Val717Phe 
 Familial 
 Paternal 
 Simplex 
 GEN229R014 
 missense_variant 
 C>T 
 p.Ala729Thr 
 Familial 
 Maternal 
 Multiplex 
 GEN229R015 
 missense_variant 
 c.3484G>A 
 p.Glu1162Lys 
  
  
  
 GEN229R016 
 missense_variant 
 C>T 
 p.Gly1170Arg 
 Familial 
 Maternal 
 Simplex 
 GEN229R017 
 missense_variant 
 c.4126G>A 
 p.Val1376Ile 
  
  
  
 GEN229R018 
 missense_variant 
 c.4605A>T 
 p.Asp1535Asn 
 Familial 
 Maternal 
 Simplex 
 GEN229R019 
 missense_variant 
 A>G 
 p.Leu1722Pro 
 Familial 
 Paternal 
 Simplex 
 GEN229R020 
 missense_variant 
 G>A 
 p.Thr410Met 
  
  
  
 GEN229R021 
 missense_variant 
 C>T 
 p.Ser557Asn 
  
  
  
 GEN229R022 
 missense_variant 
 C>T 
 p.Met1717Ile 
  
  
  
 GEN229R023 
 missense_variant 
 c.467A>G 
 p.Lys156Arg 
  
  
  
 GEN229R024 
 synonymous_variant 
 c.492C>T 
 p.(=) 
  
  
  
 GEN229R025 
 intron_variant 
 c.526+61G>A 
 N/A 
  
  
  
 GEN229R026 
 intron_variant 
 c.527-18C>A 
 N/A 
  
  
  
 GEN229R027 
 intron_variant 
 c.527-8G>T 
 N/A 
  
  
  
 GEN229R028 
 missense_variant 
 c.569G>A 
 p.Arg190His 
  
  
  
 GEN229R029 
 intron_variant 
 c.640+11C>T 
 N/A 
  
  
  
 GEN229R030 
 intron_variant 
 c.800-33C>T 
 N/A 
  
  
  
 GEN229R031 
 intron_variant 
 c.924+19G>A 
 N/A 
  
  
  
 GEN229R032 
 intron_variant 
 c.924+133G>C 
 N/A 
  
  
  
 GEN229R033 
 intron_variant 
 c.1061-81C>T 
 N/A 
  
  
  
 GEN229R034 
 intron_variant 
 c.1141+49G>A 
 N/A 
  
  
  
 GEN229R035 
 intron_variant 
 c.1148-109C>T 
 N/A 
  
  
  
 GEN229R036 
 missense_variant 
 c.1201A>C 
 p.Lys401Gln 
  
  
  
 GEN229R037 
 synonymous_variant 
 c.1284G>A 
 p.(=) 
  
  
  
 GEN229R038 
 intron_variant 
 c.302+14C>A 
 N/A 
  
  
  
 GEN229R039 
 intron_variant 
 c.1302+35G>A 
 N/A 
  
  
  
 GEN229R040 
 intron_variant 
 c.1303-54C>T 
 N/A 
  
  
  
 GEN229R041 
 missense_variant 
 c.1316G>A 
 p.Arg439His 
  
  
  
 GEN229R042 
 synonymous_variant 
 c.1392G>T 
 p.(=) 
  
  
  
 GEN229R043 
 missense_variant 
 c.1763A>G 
 p.Tyr588Cys 
  
  
  
 GEN229R044 
 synonymous_variant 
 c.1923G>A 
 p.(=) 
  
  
  
 GEN229R045 
 synonymous_variant 
 c.2052G>A 
 p.(=) 
  
  
  
 GEN229R046 
 synonymous_variant 
 c.2823C>T 
 p.(=) 
  
  
  
 GEN229R047 
 synonymous_variant 
 c.3135C>T 
 p.(=) 
  
  
  
 GEN229R048 
 synonymous_variant 
 c.3324C>T 
 p.(=) 
  
  
  
 GEN229R049 
 missense_variant 
 c.3620C>T 
 p.Pro1207Leu 
  
  
  
 GEN229R050 
 intron_variant 
 c.3843-12T>C 
 N/A 
  
  
  
 GEN229R051 
 frameshift_variant 
 c.2542insCA 
  
 De novo 
  
 Simplex 
 GEN229R052 
 synonymous_variant 
 c.132G>A 
 p.(=) 
 De novo 
  
 Simplex 
 GEN229R053 
 copy_number_loss 
  
  
 Unknown 
  
 Unknown 
 GEN229R054 
 inversion 
  
  
 De novo 
  
 Simplex 
 GEN229R055 
 translocation 
  
  
 De novo 
  
  
 GEN229R056 
 copy_number_loss 
  
  
 De novo 
  
 Simplex 
 GEN229R057 
 translocation 
  
  
 De novo 
  
  
 GEN229R058 
 nonsynonymous_variant 
  
  
 Unknown 
  
 Unknown 
 GEN229R059 
 missense_variant 
 c.1313C>T 
 p.Thr438Met 
 Familial 
 Maternal 
  
 GEN229R060 
 missense_variant 
 C>A 
 p.Gly488Val 
 Unknown 
  
  
 GEN229R061 
 missense_variant 
 c.1829C>A 
 p.Ser610Tyr 
 Unknown 
  
  
 GEN229R062 
 missense_variant 
 c.2069A>G 
 p.Asn690Ser 
 Unknown 
  
  
 GEN229R063 
 missense_variant 
 c.2872C>A 
 p.Arg958Ser 
 Unknown 
  
  
 GEN229R064 
 missense_variant 
 c.3355C>A 
 p.Pro1119Thr 
 Unknown 
  
  
 GEN229R065 
 missense_variant 
 c.3431C>T 
 p.Pro1144Leu 
 Familial 
 Maternal 
  
 GEN229R066 
 missense_variant 
 c.4822G>A 
 p.Val1608Ile 
 Familial 
 Maternal 
  
 GEN229R067 
 missense_variant 
 c.4936C>A 
 p.Leu1646Met 
 Familial 
 Maternal 
  
 GEN229R068 
 missense_variant 
 c.5191G>T 
 p.Ala1731Ser 
 Familial (n=2), unknown (n=2) 
 Maternal (n=2) 
  
 GEN229R069 
 missense_variant 
  
 p.Ala578Val 
 Familial 
 Maternal 
 Multiplex 
 GEN229R070 
 stop_gained 
 c.757C>T 
 p.Arg253Ter 
 De novo 
  
 Simplex 
 GEN229R071 
 missense_variant 
 c.3427G>A 
 p.Ala1143Thr 
 De novo 
  
 Simplex 
 GEN229R072 
 frameshift_variant 
 c.1896dupA 
 p.Asp633Argfs 
 De novo 
  
  
 GEN229R073 
 missense_variant 
 c.2518C>T 
 p.Pro840Ser 
 Familial 
 Paternal 
  
 GEN229R074 
 stop_gained 
 c.87C>G 
 p.Tyr29Ter 
 De novo 
  
 Simplex 
 GEN229R075 
 missense_variant 
 c.359C>T 
 p.Arg120Gln 
 Familial 
 Maternal 
 Simplex 
 GEN229R076 
 frameshift_variant 
 c.2540_2541del 
 p.Ser847Ter 
 De novo 
  
  
 GEN229R077 
 missense_variant 
 C>T 
 p.Glu11Lys 
 Unknown 
  
 Multiplex 

Common

Variant ID
Polymorphism
SNP ID
Allele Change
Residue Change
Population Origin
Population Stage
Author, Year
 GEN229C001 
 intron_variant 
 rs76717360 
 c.2062-22283G>A;c.298-22283G>A 
  
 226 Chinese ASD cases (188 male, 38 female) and 239 Chinese controls without ASD or other psychiatric disorders (193 males, 46 females) 
 Discovery 
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
11
Deletion
 2
 
11
Deletion
 7
 
11
Duplication
 4
 
11
Deletion-Duplication
 15
 

Model Summary

Different abnormalities in synaptic glutamate receptor expression can cause alterations in social interactions and communication.

References

Type
Title
Author, Year
Primary
Autistic-like behaviours and hyperactivity in mice lacking ProSAP1/Shank2.
Additional
Autistic-like social behaviour in Shank2-mutant mice improved by restoring NMDA receptor function.
Additional
Trans-synaptic zinc mobilization improves social interaction in two mouse models of autism through NMDAR activation.
Additional
Enhancing inhibitory synaptic function reverses spatial memory deficits in Shank2 mutant mice.
Additional
Cerebellar Shank2 Regulates Excitatory Synapse Density, Motor Coordination, and Specific Repetitive and Anxiety-Like Behaviors.
Additional
Shank2 Deletion in Parvalbumin Neurons Leads to Moderate Hyperactivity, Enhanced Self-Grooming and Suppressed Seizure Susceptibility in Mice.
Additional
Heterogeneity of Cell Surface Glutamate and GABA Receptor Expression in Shank and CNTN4 Autism Mouse Models.
Additional
Early Correction of N-Methyl-D-Aspartate Receptor Function Improves Autistic-like Social Behaviors in Adult Shank2-/- Mice.

M_SHANK2_1_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Homologous recombination mediated deletion of exon 7 of Shank2 gene.
Allele Type: Targeted (Knockout)
Strain of Origin: C57BL/6
Genetic Background: Not Specified
ES Cell Line: RI
Mutant ES Cell Line: Not specified
Model Source: Not specified

M_SHANK2_2_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Homologous recombination mediated deletion of exon 7 of Shank2 gene.
Allele Type: Targeted (Knockout)
Strain of Origin: C57BL/6
Genetic Background: Not Specified
ES Cell Line: RI
Mutant ES Cell Line: Not specified
Model Source: Not specified

M_SHANK2_3_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Targeted deletion of exons 6 and 7 and a frame shift of Shank2 gene.
Allele Type: Targeted (Knockout)
Strain of Origin: 129S4/SvJae
Genetic Background: C57BL/6*129S4
ES Cell Line: J1
Mutant ES Cell Line: Not specified
Model Source: Not specified

M_SHANK2_4_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Targeted deletion of exons 6 and 7 and a frame shift of Shank2 gene.
Allele Type: Targeted (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_SHANK2_5_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Mice homozygous for the targeted deletion of exons 6 and 7 causing a frame shift of Shank2 gene were backcrossed to a C57BL/6 background for more than 20 generations.
Allele Type: Targeted (Knockout)
Strain of Origin: 129S4/SvJae
Genetic Background: C57BL/6
ES Cell Line: J1
Mutant ES Cell Line:
Model Source:

M_SHANK2_6_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Shank2 KO mice with deleted exons 6 and 7 on a mixed background of 46 % C57Bl/6J and 54 % C57Bl/6N.
Allele Type: Targeted
Strain of Origin: C57Bl/6N
Genetic Background: C57Bl/6J * C57Bl/6N
ES Cell Line: Unreported
Mutant ES Cell Line: Unreported
Model Source: Seoul National University

M_SHANK2_7_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Shank2 KO mice with deleted exon 7 on a mixed background of 75 % C57Bl/6J and 25 % C57Bl/6N.
Allele Type: Targeted
Strain of Origin: C57Bl/6J
Genetic Background: C57Bl/6J * C57Bl/6N
ES Cell Line: Unreported
Mutant ES Cell Line: Unreported
Model Source: Seoul National University

M_SHANK2_8_CKO_HM_PurkinjeN

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Conditional deletion of exons 6 and 7 of the Shank2 gene using L7-cre, in the Purkinje cells of the cerebellum
Allele Type: Conditional loss-of-function
Strain of Origin: C57BL/6J
Genetic Background: C57BL/6J
ES Cell Line: J1
Mutant ES Cell Line: Not specified
Model Source: Biocytogen

M_SHANK2_9_CKO_HM_PvalbN

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Conditional deletion of exons 6-7 of the Shank2 gene using Pvalb-cre, in parvalbumin expressing interneurons
Allele Type: Conditional loss-of-function
Strain of Origin: C57BL/6J
Genetic Background: C57BL/6J*129P2/OlaHsd
ES Cell Line: Not specified
Mutant ES Cell Line: Not specified
Model Source: 27903723; JacksonLaboratory, #8069 (Pv-Cre): B6;129P2-Pvalb^tm1(cre)Arbr/J

M_SHANK2_10_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Mice homozygous for targeted deletion of exon 24.
Allele Type: Targeted (Knockout)
Strain of Origin: Not specified
Genetic Background: Not specified
ES Cell Line: Not specified
Mutant ES Cell Line:
Model Source: Duke University, PMID 29046483

M_SHANK2_11_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Mice homozygous for the targeted deletion of exons 6 and 7 causing a frame shift of Shank2 gene were backcrossed to a C57BL/6 background for more than 20 generations.
Allele Type: Targeted (Knockout)
Strain of Origin: 129S4/SvJae
Genetic Background: C57BL/6J
ES Cell Line: J1
Mutant ES Cell Line:
Model Source: Korea Advanced Institute of Science and Technology (KAIST)

M_SHANK2_1_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Righting response1
Decreased
Description: Decreased righting response as measured by increased latency to right up
Exp Paradigm: Female mice: Righting reflex
 Righting reflex test
 P8
Limb Posture1
Abnormal
Description: Abnormal limb posture indicated by hindlimb clasping
Exp Paradigm: Tail hanging assay
 Tail suspension test
 4 months
General locomotor activity1
Increased
Description: Increased locomotor activity as measured by distance traveled and number of transitions
Exp Paradigm: Open field test, 3 chamber test, Y maze test
 Open field test
 Unreported
Righting response1
Increased
Description: Increased righting response as measured by decreased latency to right up
Exp Paradigm: Male mice: Righting reflex
 Righting reflex test
 P4, P10
Neuroreceptor levels: GABA-R: GABAA2
Decreased
Description: Mutants show decreased cell surface GABA(A)-Ra1 in the thalamus compared to controls. Mutants show no change in the total expression of analyzed recpetors.
 Western blot
 3-6 months
Neuroreceptor levels: glutamate receptors: NMDA receptors2
Decreased
Description: Mutants show reduced expression of cell surface GluN1 compared to controls, in the striatum, cortex, and thalamus. Mutants show no change in the total expression of analyzed recpetors.
 Western blot
 3-6 months
Dendritic architecture: spine density1
Decreased
Description: Decreased spine numbers in CA1 region of hippocampus
Exp Paradigm: Golgi-Cox staining of CA1 hippocampal neurons
 Golgi-Cox staining
 Unreported
Neuroreceptor levels: glutamate receptors: NMDA receptors2
Increased
Description: Mutants show increased expression of cell surface GluN1 compared to controls, in the hippocampus. Mutants show no change in the total expression of analyzed recpetors.
 Western blot
 3-6 months
Neuroreceptor levels: glutamate receptors: AMPA receptors2
Decreased
Description: Mutants show decreased cell surface mGluR5 in the hippocampus, and GluA2 in the cerebellum, compared to controls. Mutants show no change in the total expression of analyzed recpetors.
 Western blot
 3-6 months
Miniature post synaptic current frequency: excitatory3
Decreased
Description: Mutants show decrease in mEPSC frequency at Schaffer collateral-CA1 pyramidal synapses at 3-4 weeks compared with controls.
 Whole-cell patch clamp: CA1
 3-4 weeks
Synaptic plasticity1
Increased
Description: Increased synaptic plasticity indicated by enhanced long-term potentiation induced by hig h frequency stimulation of Schaffer collaterals
Exp Paradigm: Whole-cell patch clamp recordings of long-term potentiation induced by a single tetanus of 100 pulses at 100 Hz
 Whole-cell patch clamp
 Unreported
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission3
Increased
Description: Mutants show increase in NMDA/AMPA ratio at Schaffer collateral-CA1 pyramidal synapses at 3-4 weeks but not at 2 weeks compared with control.
 Whole-cell patch clamp: CA1
 3-4 weeks, 2 weeks
Synaptic transmission1
Decreased
Description: Decreased synaptic transmission indicated by reduction in miniature excitatory postsynaptic currents (mEPSC) frequency
Exp Paradigm: Whole-cell patch clamp recordings from CA1 pyramidal cells
 Whole-cell patch clamp
 Unreported
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission1
Increased
Description: Increased NMDA/AMPA ratio
Exp Paradigm: Whole-cell patch clamp recordings from CA1 pyramidal cells of compound EPSCs were evoked at -60 and +40 mV
 Whole-cell patch clamp
 Unreported
Synaptic transmission1
Decreased
Description: Decreased synaptic transmission demonstrated by decreased field excitatory postsynaptic potentials (fEPSPs)
Exp Paradigm: Extracellular field and whole-cell patch clamp recordings from CA1 pyramidal cells in acute hippocampal slices
 Field potential recordings
 3-4, 13 weeks
Self grooming: perseveration1
Increased
Description: Increased self grooming behavior
Exp Paradigm: Grooming behavior assessments in female mice
 Grooming behavior assessments
 Unreported
Repetitive digging1
Decreased
Description: Decreased digging behavior
 
 Unreported
Social interaction1
Decreased
Description: Decreased social novelty demonstrated by reduction in recognition and interest for social novelty
Exp Paradigm: Three chambered test
 Three-chamber social approach test
 Unreported
Social interaction1
Decreased
Description: Decreased social interactions indicated by difficulty maintaining social contacts
Exp Paradigm: Free same-sex social interactions (residentintruder),
 Resident-intruder test
 Unreported
Social interaction1
Decreased
Description: Decreased social interaction indicated by increased latency for first contact
Exp Paradigm: Free interactions of a tested male mouse with an oestrus C57BL/6 female mouse
 Reciprocal social interaction test: male-female in estrus interaction
 Unreported
Ultrasonic vocalization1
Decreased
Description: Decreased ultrasonic vocalizations indicated by longer latency to emit first vocalization as well as short and unstructured calls during male-esterous female interactions
Exp Paradigm: Ultrasonic Vocalization (USV) during male-esterous female free interaction
 Monitoring ultrasonic vocalizations: reciprocal social interaction test: male-female
 Unreported
Ultrasonic vocalization1
Increased
Description: Increased ultrasonic vocalization call rate
Exp Paradigm: Female mice: Pup isolation calls
 Monitoring ultrasonic vocalizations: maternal separation
 P4, P10
Ultrasonic vocalization1
Decreased
Description: Decreased ultrasonic vocalizations indicated by longer latency to emit first vocalization, fewer vocalization plus short and unstructured calls during female-female interactions
Exp Paradigm: Ultrasonic Vocalization (USV) during female-female free interaction
 Monitoring ultrasonic vocalizations: reciprocal social interaction test
 Unreported
Size/growth1
Decreased
Description: Decreased body weight
Exp Paradigm: Female mice: General observations
 General observations
 2 weeks
Size/growth1
Decreased
Description: Decreased body weight
Exp Paradigm: General observations
 General observations
 3, 17 weeks
Anxiety1
Increased
Description: Increased anxiety demonstrated by decreased latency to enter and increased proportion time spent in dark compartment
Exp Paradigm: Light-dark box test
 Light-dark exploration test: Light-dark exploration test
 Unreported
Gene expression: alternative splicing3
Increased
Description: Mutants show increased shorter Shank2a splice variant compared with controls.
 Quantitative PCR (qRT-PCR)
 3.6-4 weeks
Protein expression level evidence1
Increased
Description: Increased NMDAR subunit levels in hippocampus and striatum
Exp Paradigm: Nmdar Subnit Levels
 Western blot
 3.5 weeks
Gene expression: alternative splicing3
Decreased
Description: Mutants show decreased levels of longer Shank2b splice variant compared with controls.
 Quantitative PCR (qRT-PCR)
 3.6-4 weeks
Protein expression level evidence1
Increased
Description: Increased NMDAR subunit levels in cortex, hippocampus and striatum
Exp Paradigm: Nmdar Subnit Levels
 Western blot
 10 weeks
Protein expression level evidence1
Increased
Description: Increased levels of N-methyl-D- aspartate receptor (NMDAR) subunit GluN1 and ProSAP2/Shank3 in whole brain PSDs
Exp Paradigm: Nmdar Subnit Levels
 Western blot
 Unreported
Protein expression level evidence1
Increased
Description: Increased synaptic content of ionotropic glutamate receptor
Exp Paradigm: Ionotropic Glutamate Receptor Content
 
 Unreported
Ultrasonic vocalization1
 No Change
 Monitoring ultrasonic vocalizations: maternal separation
 P4, P10
Ultrasonic vocalization1
 No Change
 Monitoring ultrasonic vocalizations: reciprocal social interaction test
 Unreported
Size/growth1
 No Change
 General observations
 2 weeks
Object recognition memory1
 No Change
 Novel object recognition test
 Unreported
Spatial working memory1
 No Change
 Y-maze test
 Unreported
Protein expression level evidence1
 No Change
 Quantitative PCR (qRT-PCR)
 Unreported
Protein expression level evidence1
 No Change
 Western blot
 Unreported
Motor coordination and balance1
 No Change
 Accelerating rotarod test
 6-8 months
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
Miniature post synaptic current amplitude: excitatory3
 No Change
 Whole-cell patch clamp: CA1
 3-4 weeks
Synaptic plasticity: LTD1
 No Change
 Whole-cell patch clamp
 Unreported
Synaptic transmission1
 No Change
 Whole-cell patch clamp
 Unreported
Synaptic transmission1
 No Change
 
 Unreported
Synaptic transmission1
 No Change
 Whole-cell patch clamp
 Unreported
Olfaction1
 No Change
 Buried food test
 Unreported
Olfaction1
 No Change
 Home cage odor preference test: pups
 P7
 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_SHANK2_2_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Protein expression level evidence1
Increased
Description: Increased NMDAR subunit levels in hippocampus and striatum
Exp Paradigm: Nmdar Subnit Levels
 Western blot
 3.5 weeks
Object recognition memory1
 No Change
 Novel object recognition test
 Unreported
Spatial working memory1
 No Change
 Y-maze test
 Unreported
Righting response1
 No Change
 Righting reflex test
 P4, P8, P10
Olfaction1
 No Change
 Buried food test
 Unreported
Olfaction1
 No Change
 Home cage odor preference test: pups
 P7
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Maternal behavior, Neuroanatomy / Ultrastructure / Cytoarchitecture, Neurophysiology, Repetitive behavior, Seizure, Social behavior

M_SHANK2_3_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Motor coordination and balance2
Decreased
Description: Shank2 homozygous knockout mice show reduced motor coordination measured by an increased frequency of missteps, compared with wildtype mice.
Exp Paradigm: Males only.
 Erasmus ladder test
 Unreported
General locomotor activity1
Increased
Description: Increased locomotor activity indicative of hyperactivity measured as the distance traveled
Exp Paradigm: Open field test
 Open field test
 2-5 months
General locomotor activity1
Increased
Description: Increased locomotor activity indicative of hyperactivity measured as the distance traveled
Exp Paradigm:  Elevated plus maze test
 Elevated plus maze test
 2-5 months
Synapse density: Excitatory2
Decreased
Description: Shank2 homozygous knockout mice show altered contact and alignment of the postsynaptic density with presynaptic axon terminals, and decreased density of excitatory synapses, compared to wild type controls.
Exp Paradigm: Altered synaptic alignment was measured by number of free spines that were not in close contact with the presynaptic nerve terminals and number of mismatched excitatory synapses, in which the postsynaptic density was misaligned with the presynaptic nerve terminal.
 Electron microscopy: Cerebellar Purkinje cell and parallel fiber synapses
 2.7-3.3 weeks
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission1
Decreased
Description: Decreased NMDA/AMPA ratio at SC-CA1 synapses
Exp Paradigm: Extracellular recordings of NMDAR and AMPAR transmission
 Field potential recordings
 3-4 weeks
Miniature post synaptic current frequency: excitatory2
Decreased
Description: Shank2 homozygous knockout mice show reduced frequency of mEPSPs compared to wild type control mice.
Exp Paradigm: Males and females tested.
 Whole-cell patch clamp: Purkinje cell and parallel fiber synapses
 2.7-3.3 weeks
Synaptic plasticity: LTD1
Decreased
Description: Decreased long-term depression (LTD) induced by low-frequency stimulation at SC-CA1 synapses
Exp Paradigm: Extracellular recordings at hippocampal Schaffer-collateral-CA1-pyramidal synapses of LTD induced by DHPG
 Field potential recordings
 5-6 weeks
Synaptic plasticity1
Decreased
Description: Decreased synaptic plasticity indicative of impaired long-term potentiation at SC-CA1 synapses
Exp Paradigm: Extracellular recordings at hippocampal Schaffer-collateral-CA1-pyramidal synapses of LTP induced by theta-burst stimulation
 Field potential recordings
 8-9 weeks
Self grooming: perseveration1
Increased
Description: Increased self grooming behavior
Exp Paradigm: Grooming behavior assessments during object recognition test
 Novel object recognition test
 2-5 months
Repetitive digging1
Decreased
Description: Decreased digging behavior
Exp Paradigm: Observation of repetitive behavior in home cage
 Home cage behavior
 2-5 months
Vertical jumping or back flipping1
Increased
Description: Increased repetitive jumping behavior mostly mixed with upright scrabbling
Exp Paradigm: Observation of repetitive behavior in home cage
 Observation of repetitive behavior
 2-5 months
Social interaction1
Decreased
Description: Decreased social interaction demonstrated by decreased preference to explore novel mouse over inanimate object
Exp Paradigm: Three-chambered social interaction assay between novel mouse and inanimate object
 Three-chamber social approach test
 4-5 weeks
Nest building behavior1
Decreased
Description: Decreased nest building behavior
Exp Paradigm: Nest building assay
 Nest building assay
 2-5 months
Social interaction1
Decreased
Description: Decreased social interaction with normal target mice
Exp Paradigm: Home-cage social interaction assay
 Reciprocal social interaction test
 2-5 months
Ultrasonic vocalization1
Decreased
Description: Decreased ultrasonic vocalizations as indicated by longer latency and lower frequency of calls
Exp Paradigm: Ultrasonic Vocalization (USV) during interaction of male with novel female
 Monitoring ultrasonic vocalizations: reciprocal social interaction test: male-female
 2-5 months
Anxiety1
Increased
Description: Increased anxiety shown by decreased time spent in open arms, increased time spent in closed arms, and increased number of closed, but not open, arm entries
Exp Paradigm: Elevated plus maze test
 Elevated plus maze test
 2-5 months
Spatial learning1
Decreased
Description: Decreased spatial learning as indicated by reduced amount of time in target quadrant and less frequency of crossing platform area
Exp Paradigm: Morris water maze test
 Morris water maze test
 2-5 months
Pup retrieval1
Decreased
Description: Decreased pup retrieval efficiency of female mice
Exp Paradigm: Pup retrieval assay
 Pup retrieval assay
 2-5 months
Protein localization: cytosol2
Decreased
Description: Shank2 homozygous knockout mice show reductions in the levels of cytoplasmic proteins such as PSD-95, PSD-93, and Homer, compared to wild type controls.
Exp Paradigm: Males and females tested.
 Western blot: cerebellum, synaptosomal
 2.7-3.3 weeks
Targeted expression2
Decreased
Description: Shank2 homozygous knockout mice show no expression of Shank2 protein in total cerebellar lysates or cerebellar Shank2 localized at the molecular cell layer of the cerebellar cortex, at parallel fiber excitatory synapses or in the dendrites of Purkinje cells as seen in wild type controls.
Exp Paradigm: Calbindin was used to label Purkinje cells. VGluT1 and VGAT were used as excitatory and inhibitory synaptic markers, respectively. Males and females tested.- Western blot: Cerebellum
 Western blot: Cerebellum
 Adult
Protein expression level evidence2
Decreased
Description: Shank2 homozygous knockout mice show reduced total levels of the cerebellar proteins, GluD2, GluA2, GluA2/3, GluN1, mGluR1, PSD93, Homer, IP3R, CAMKIIa/b, Neurolignin1, vGLUT1, and cerebellar inhibitory synaptic proteins (gephyrin, VGAT, and GAD65) compared to wild type controls.
Exp Paradigm: Males and females tested.
 Western blot: cerebellum
 2.7-3.3 weeks
Signaling1
Decreased
Description: Decreased NMDAR associated signaling indicated by lower levels of phosphorylated CaMKII-alpha/beta, ERK1/2 , p38, GluA1 (S831 and S845)
Exp Paradigm: Nmdar Associated Signaling
 Western blot
 3-4 weeks
Protein expression level evidence1
Decreased
Description: Decreased Shank2 protein expression in synaptic fractions
Exp Paradigm: Shank2 Protein Expression
 Western blot
 2-3 months
Protein localization: synapse2
Decreased
Description: Shank2 homozygous knockout mice show reductions in the levels of excitatory synaptic membrane proteins, including GluD2, the NMDA receptor subunit GluN2C, and AMPA receptor subunits (GluA1 and GluA2), compared to wild type control mice.
Exp Paradigm: Crude Synaptosomal and total synaptic proteins were measured. Males and females tested.
 Western blot: cerebellum, synaptosomal
 2.7-3.3 weeks
Gene expression1
Decreased
Description: Decreased Shank2 mRNA levels in brain
Exp Paradigm: Shank2 Mrna Levels
 Quantitative PCR (qRT-PCR)
 Unreported
Targeted expression2
Decreased
Description: Shank2 homozygous knockout mice show no expression of Shank2 protein in total cerebellar lysates or cerebellar Shank2 localized at the molecular cell layer of the cerebellar cortex, at parallel fiber excitatory synapses or in the dendrites of Purkinje cells as seen in wild type controls.
Exp Paradigm: Calbindin was used to label Purkinje cells. VGluT1 and VGAT were used as excitatory and inhibitory synaptic markers, respectively. Males and females tested.-Immunofluorescence staining
 Immunofluorescence staining
 Adult
Reproductive system development1
 No Change
 General observations
 Unreported
Anxiety1
 No Change
 Light-dark exploration test: Light-dark exploration test
 2-5 months
Anxiety1
 No Change
 Open field test
 2-5 months
Anxiety2
 No Change
 Light-dark exploration test: Light-dark exploration test
 35 months
Protein expression level evidence1
 No Change
 Western blot
 3-4 weeks
Protein expression level evidence2
 No Change
 Western blot: cerebellum
 2.7-3.3 weeks
Signaling1
 No Change
 Western blot
 3-4 weeks
Brain cytoarchitecture1
 No Change
 Electron microscopy
 8-9 weeks
Brain cytoarchitecture1
 No Change
 Immunohistochemistry: fluorescence
 3 months
Brain morphology1
 No Change
 Immunohistochemistry: fluorescence
 Unreported
Neuronal number: Purkinje cells1
 No Change
 
 Unreported
Post-synaptic density size2
 No Change
 Electron microscopy: Cerebellar Purkinje cell and parallel fiber synapses
 2.7-3.3 weeks
Miniature post synaptic current amplitude: excitatory2
 No Change
 Whole-cell patch clamp: Purkinje cell and parallel fiber synapses
 2.7-3.3 weeks
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission1
 No Change
 Field potential recordings
 3-4 weeks
Synaptic plasticity: cerebellar LTD2
 No Change
 Whole-cell patch clamp: Purkinje cell and parallel fiber synapses
 2.7-3.3 weeks
Synaptic transmission1
 No Change
 Field potential recordings
 8-9 weeks
Repetitive nose pokes2
 No Change
 Hole-board test
 35 months
Self grooming: perseveration1
 No Change
 Novel object recognition test: measurement of self grooming
 2-5 months
Olfaction1
 No Change
 Three-chamber social approach test: sociability
 2-5 months
Social interaction1
 No Change
 Three-chamber social approach test
 4-5 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Homeostasis, Immune response, Learning & memory, Maternal behavior, Seizure, Sensory, Social behavior

M_SHANK2_4_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
General locomotor activity1
Increased
Description: Increased locomotor activity indicative of hyperactivity
Exp Paradigm:  Elevated plus maze test
 Elevated plus maze test
 2-5 months
General locomotor activity1
Increased
Description: Increased locomotor activity indicative of hyperactivity
Exp Paradigm: Open field test
 Open field test
 2-5 months
Anxiety1
 No Change
 Elevated plus maze test
 2-5 months
Object recognition memory1
 No Change
 Novel object recognition test
 2-5 months
Repetitive digging1
 No Change
 Home cage behavior
 2-5 months
Self grooming: perseveration1
 No Change
 Novel object recognition test
 2-5 months
Vertical jumping or back flipping1
 No Change
 Observation of repetitive behavior
 2-5 months
Social interaction1
 No Change
 Three-chamber social approach test
 4-5 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Homeostasis, Immune response, Maternal behavior, Molecular profile, Neuroanatomy / Ultrastructure / Cytoarchitecture, Neurophysiology, Seizure, Sensory

M_SHANK2_5_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
General locomotor activity: Ambulatory activity2
Increased
Description: Mutants show increased total distance moved compared with controls.
 Open field test
 Adult
Hyperactivity: Home cage/familiar environment2
Increased
Description: Mutants show increased total distance moved compared with controls.
 Home cage behavior
 Adult
Hyperactivity1
Increased
Description: Shank 2 null mice show increased activity levels in the open field test
 Open field test
 2-4 months
Neuroreceptor levels: glutamate receptors: NMDA receptors2
Abnormal
Description: Mutants show increased brain protein levels of phosphorylated S896-GluN1 and S-1303-GluN2B at 2 weeks. Mutants show decreased brain protein levels of phosphorylated S896-GluN1 and S-1303-GluN2B at 2 weeks. Mutants show no change in total GluN1, GluN2B, GluN2A, GluN3A, or GluN2B phosphorylated at any other residue, at 2 and 3 weeks.
 Western blot
 2, 3 weeks
Decay kinetics of miniature post synaptic currents2
Decreased
Description: Mutants show slower decay kinetics of NMDAR currents and increased sensitivity of the NMDAR currents to the GluN2B specific inhibitor ifenprodil, compared with controls, indicating that the increased NMDAR function involves mainly the GluN2B subunit.
 Whole-cell patch clamp
 2 weeks
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission2
Increased
Description: Mutants show an increase of the ratio of NMDAR/AMPAR mediated synaptic transmission at Schaffer collateral-CA1 pyramidal synapses and at layer II/III pyramidal neurons in the medial prefrontal cortex at P14 compared with controls.
 Whole-cell patch clamp
 2 weeks, 3.6 weeks
Miniature post synaptic current frequency: excitatory2
Decreased
Description: Mutants show decreased mEPSC frequency in the medial prefrontal cortex but no change in mEPSC frequency in CA1 pyramidal neurons compared with controls.
 Whole-cell patch clamp
 2, 3-3.9 weeks
EPSP-spike relationship2
Decreased
Description: Mutants show decrease in fEPSP slope at P25 and adulthood compared with controls.
 Whole-cell patch clamp
 3.6 weeks, Adult
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission2
Decreased
Description: Mutants show decrease in NMDA/AMPA ratio at Schaffer CA1 synapses and at layer II/III pyramidal neurons in the medial prefrontal cortex compared with controls.
 Whole-cell patch clamp
 3-3.9 weeks
Vertical jumping or back flipping2
Increased
Description: Mutants show increase in time spent jumping compared with controls.
 Home cage behavior
 Adult
Self grooming: perseveration2
Increased
Description: Mutants show increase in time spent self grooming compared with controls.
 Home cage behavior
 Adult
Repetitive digging2
Decreased
Description: Mutants show decrease in digging duration compared with controls.
 Home cage behavior
 Adult
Vertical jumping or back flipping1
Increased
Description: Shank 2 null mice show increased jumping in their home cage compared to controls
 Home cage behavior
 2-4 months
Social approach1
Decreased
Description: Shank 2 null mice have reduced sociabilityor preference towards a stranger mouse in the three chamber social approach test.
 Three-chamber social approach test: time spent in exploration or sniffing
 2-4 months
Social interaction2
Decreased
Description: Mutants show decreased social interaction compared with controls.
 Reciprocal social interaction test
 4-5 weeks
Social approach2
Decreased
Description: Mutants show decreased sociability compared with controls.
 Three-chamber social approach test
 Adult
Social dominance2
Decreased
Description: Mutants show increased submissiveness in urine tests compared with controls. Increased submissiveness in mutants did not correlate with social interaction.
 Dominance hierarchy formation
 Adult
Social dominance2
Decreased
Description: Mutants show increased submissiveness in the tube test compared with controls. Increased submissiveness in mutants did not correlate with social interaction.
 Tube test of social dominance
 Adult
Ultrasonic vocalization: Interaction induced: opposite sex stimulus2
Decreased
Description: Mutants males show decrease in ultrasonic vocalization compared with controls.
 Monitoring ultrasonic vocalizations
 Adult
Anxiety1
Increased
Description: Shank 2 null mice have increased anxiety-like behavior as they spend significantly reduced time in the center of the open field
 Open field test
 2-4 months
Anxiety2
Decreased
Description: Mutants spend more time in the open arms and less time in the closed arms compared with controls.
 Elevated plus maze test
 Adult
Signaling2
Increased
Description: Mutants show increase in the brain protein levels of CaMKIIalpha at 3 but not 2 weeks. Mutants show no change in brain protein levels of phosphorylated CaMKIIalpha or beta or total CaMKIIbeta at 2 or 3 weeks.
 Western blot
 2, 3 weeks
Gene expression2
Abnormal
Description: Mutants show 16 differentially expressed genes (DEGs) in the brain at P14 and 35 at P25 compared with controls. DEGs were associated with ribosome, translation, excitatory post synaptic compartments, excitatory synapse, postsynaptic membrane, and post synaptic density. Mutants show enrichment of genes associated with NMDAR activation and NMDAR dependent LTP and LTD.
 RNA sequencing
 2 weeks, 3 weeks, 3.6 weeks
Protein phosphorylation2
Increased
Description: Mutants show increase in brain levels of phosphorylated CREB at 2 but not 3 weeks. Mutants show no change in brain protein levels of total CREB at 2 or 3 weeks compared with controls.
 Western blot
 2, 3 weeks
Signaling: PKC pathway2
Decreased
Description: Mutants show decreased brain protein levels of total PKCalpha at 3 but not 2 weeks. Mutants show no change in brain protein levels of phosphorylated PKCalpha at 2 or 3 weeks.
 Western blot
 2, 3 weeks
Protein expression level evidence2
Decreased
Description: Mutants show no change in brain protein levels of phosphorylated PKA compared with controls at 2 or 3 weeks. Mutants show decrease in brain protein levels of PKA at 2 but not 3 weeks.
 Western blot
 2, 3 weeks
Signaling: MAPK pathway2
Abnormal
Description: Mutants show increase in brain protein levels of phosphorylated ERK1 at 2 but not 3 weeks. Mutants show no change in total ERK1, phosphorylated ERK2, and total ERK2 at 2 or 3 weeks. Mutants show decrease in phosphorylated p38 at 3 but not 2 weeks. Mutants show decrease in total p38 at 2 but not 3 weeks.
 Western blot
 2, 3 weeks
Gene expression: alternative splicing2
Decreased
Description: Mutants show indetectable shorter Shank2a splice variant and decreased levels of longer Shank2b splice variant compared with controls.
 Quantitative PCR (qRT-PCR)
 3.6-4 weeks
Anxiety2
 No Change
 Open field test
 Adult
Signaling: mTOR pathway2
 No Change
 Western blot
 2, 3 weeks
Self grooming: home cage/familiar environment1
 No Change
 Home cage behavior
 2-4 months
Neuroreceptor levels: glutamate receptors: AMPA receptors2
 No Change
 Western blot
 2, 3 weeks
Decay kinetics of miniature post synaptic currents2
 No Change
 Whole-cell patch clamp
 3.4 weeks
EPSP-spike relationship2
 No Change
 Whole-cell patch clamp
 2, 3-3.9 weeks
Miniature post synaptic current amplitude: excitatory2
 No Change
 Whole-cell patch clamp
 2, 3-3.9 weeks
Miniature post synaptic current amplitude: inhibitory2
 No Change
 Whole-cell patch clamp
 2, 3-3.9 weeks
Miniature post synaptic current frequency: inhibitory2
 No Change
 Whole-cell patch clamp
 2, 3-3.9 weeks
Presynaptic function: paired-pulse facilitation2
 No Change
 Whole-cell patch clamp
 2, 3-3.9 weeks
Olfaction2
 No Change
 Olfactory discrimination test
 Adult
Social memory1
 No Change
 Three-chamber social approach test: time spent in exploration or sniffing stranger mouse
 2-4 months
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Homeostasis, Immune response, Learning & memory, Maternal behavior, Molecular profile, Neuroanatomy / Ultrastructure / Cytoarchitecture, Neurophysiology, Seizure, Sensory

M_SHANK2_6_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
General locomotor activity: Ambulatory activity1
Increased
Description: Shank2 exon 6-7 KO mice showed longer total distance travelled in the elevated zero-maze and open-field test, showing that the KO mice are hyperactive compared to wildtype controls
Exp Paradigm: Movement was tracked for 5 min under bright lights using EthoVision 9.0, Nodulus.-Elevated zero maze test
 Elevated zero maze test
 1.8-3.5 months
General locomotor activity: Ambulatory activity1
Increased
Description: Shank2 exon 6-7 KO mice showed longer total distance travelled in the elevated zero-maze and open-field test, showing that the KO mice are hyperactive compared to wildtype controls
Exp Paradigm: Movement was tracked for 5 min under bright lights using EthoVision 9.0, Nodulus.- Open field test
 Open field test
 1.8-3.5 months
Synaptic transmission: inhibitory1
Decreased
Description: Shank2 exon 6-7 KO mice show decreased input-output relationships of GABAergic inhibitory current and decreased inhibitory/excitatory current ratios in CA1 neurons, compared to WT littermates
Exp Paradigm: GABAA-R mediated currents were recorded from CA1 pyramidal neurons by holding at 0mV in AP5 and CNQX-containing ACSF. Stimulation intensity was adjusted to obtain approximately 300 pA of GABA current.
 Whole-cell patch clamp: CA1
 45-weeks
Social approach1
Decreased
Description: Shank2 exon 6-7 KO mice show decreased social approach measured by reduced time spent exploring a stranger mouse compared to WT littermates
Exp Paradigm: Exploration time for the cup with a block (Object) and the cup with a stranger mouse (Stranger) was measured.
 Three-chamber social approach test
 1.8-3.5 months
Anxiety1
Increased
Description: Shank2 exon 6-7 KO mice showed a significant increase in anxiety in the open field paradigm measured by increased time spent in the periphery, compared to wildtype controls.
Exp Paradigm: Movement was tracked for 5 min under bright lights using EthoVision 9.0, Nodulus.
 Open field test
 1.8-3.5 months
Spatial reference memory1
Decreased
Description: Shank2 exon 6-7 KO mice show decreased ability to find the removed platform during probe trial by swimming randomly whereas WT control mice spend more time in the target quadrant.
Exp Paradigm: Learning curve during 6 days of training in the Morris water maze task plotted latency for mice to reach the platform. Probe tests were performed as training trials with no platform and the mice were tracked for 60s.
 Morris water maze test
 1.8-3.5 months
Spatial learning1
Decreased
Description: Shank2 exon 6-7 KO mice showed a significant deficit in spatial learning during training sessions compared to wildtype controls.
Exp Paradigm: Learning curve during 6 days of training in the Morris water maze task plotted latency for mice to reach the platform.
 Morris water maze test
 1.8-3.5 months
Gene expression1
Decreased
Description: Shank2 exon 6-7 KO mice show reduced transcription of Gabra5 and Grin1 compared to wildtype controls.
Exp Paradigm: Total RNA was extracted in Trizol. Raw sequence data were mapped onto the mouse genome reference mm10 using GSNAP. Cufflinks package was used to identify differentially expressed genes (DEGs, greater than 1.5 fold difference). To assess expression levels of genes, the RPKM (reads per kilobase of exon per million mapped reads) measure was calculated. PANTHER and GO were used to classify DEGs into functional protein classes. GAPDH internal control was used in qRT-PCR.- Quantitative PCR (qRT-PCR)
 Quantitative PCR (qRT-PCR)
 4 weeks
Protein expression level evidence1
Decreased
Description: Shank2 exon 6-7 KO mice show reduced protein expression of GABA-A receptor alpha2 subunit in the hippocampus, compared to WT
 Western blot: Hippocampus
 4 weeks
Gene expression1
Decreased
Description: Shank2 exon 6-7 KO mice show reduced transcription of Gabra5 and Grin1 compared to wildtype controls.
Exp Paradigm: Total RNA was extracted in Trizol. Raw sequence data were mapped onto the mouse genome reference mm10 using GSNAP. Cufflinks package was used to identify differentially expressed genes (DEGs, greater than 1.5 fold difference). To assess expression levels of genes, the RPKM (reads per kilobase of exon per million mapped reads) measure was calculated. PANTHER and GO were used to classify DEGs into functional protein classes. GAPDH internal control was used in qRT-PCR.-RNA sequencing: Hippocampus
 RNA sequencing: Hippocampus
 4 weeks
Anxiety1
 No Change
 Elevated zero maze test
 1.8-3.5 months
Gene expression1
 No Change
 Quantitative PCR (qRT-PCR)
 4 weeks
Gene expression1
 No Change
 RNA sequencing: Hippocampus
 4 weeks
Swimming ability1
 No Change
 Morris water maze test
 1.8-3.5 months
Miniature post synaptic current amplitude: inhibitory1
 No Change
 Whole-cell patch clamp
 45-weeks
Miniature post synaptic current frequency: inhibitory1
 No Change
 Whole-cell patch clamp
 45-weeks
Presynaptic function: paired-pulse facilitation1
 No Change
 Whole-cell patch clamp: CA1, for IPSCs
 45-weeks
Spontaneous post synaptic event amplitude: inhibitory currents1
 No Change
 Whole-cell patch clamp
 45-weeks
Spontaneous post synaptic event frequency: inhibitory currents1
 No Change
 Whole-cell patch clamp
 45-weeks
Synaptic transmission: excitatory1
 No Change
 Whole-cell patch clamp
 45-weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Homeostasis, Immune response, Maternal behavior, Neuroanatomy / Ultrastructure / Cytoarchitecture, Repetitive behavior, Seizure, Sensory

M_SHANK2_7_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Spatial learning1
Decreased
Description: Shank2 exon 7 KO mice showed a significant deficit in spatial learning during training sessions compared to wildtype controls.
Exp Paradigm: Learning curve during 6 days of training in the Morris water maze task plotted latency for mice to reach the platform.
 Morris water maze test
 1.8-3.5 months
Spatial reference memory1
Decreased
Description: Shank2 exon 7 KO mice show decreased ability to find the removed platform during probe trial by swimming randomly whereas WT control mice spend more time in the target quadrant.
Exp Paradigm: Learning curve during 6 days of training in the Morris water maze task plotted latency for mice to reach the platform. Probe tests were performed as training trials with no platform and the mice were tracked for 60s.
 Morris water maze test
 1.8-3.5 months
Gene expression1
Increased
Description: Shank2 exon 6-7 KO mice show increased transcription of Gria1 and Dlg4 compared to wildtype controls.
Exp Paradigm: Total RNA was extracted in Trizol. Raw sequence data were mapped onto the mouse genome reference mm10 using GSNAP. Cufflinks package was used to identify differentially expressed genes (DEGs, greater than 1.5 fold difference). To assess expression levels of genes, the RPKM (reads per kilobase of exon per million mapped reads) measure was calculated. PANTHER and GO were used to classify DEGs into functional protein classes. GAPDH internal control was used in qRT-PCR.-RNA sequencing: Hippocampus
 RNA sequencing: Hippocampus
 4 weeks
Gene expression1
Increased
Description: Shank2 exon 6-7 KO mice show increased transcription of Gria1 and Dlg4 compared to wildtype controls.
Exp Paradigm: Total RNA was extracted in Trizol. Raw sequence data were mapped onto the mouse genome reference mm10 using GSNAP. Cufflinks package was used to identify differentially expressed genes (DEGs, greater than 1.5 fold difference). To assess expression levels of genes, the RPKM (reads per kilobase of exon per million mapped reads) measure was calculated. PANTHER and GO were used to classify DEGs into functional protein classes. GAPDH internal control was used in qRT-PCR.- Quantitative PCR (qRT-PCR)
 Quantitative PCR (qRT-PCR)
 4 weeks
Gene expression1
 No Change
 Quantitative PCR (qRT-PCR)
 4 weeks
Gene expression1
 No Change
 RNA sequencing: Hippocampus
 4 weeks
Swimming ability1
 No Change
 Morris water maze test
 1.8-3.5 months
Synaptic transmission: excitatory1
 No Change
 Whole-cell patch clamp
 45-weeks
Synaptic transmission: inhibitory1
 No Change
 Whole-cell patch clamp: CA1
 45-weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Homeostasis, Immune response, Maternal behavior, Neuroanatomy / Ultrastructure / Cytoarchitecture, Repetitive behavior, Seizure, Sensory, Social behavior

M_SHANK2_8_CKO_HM_PurkinjeN

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Motor coordination and balance1
Decreased
Description: Shank2 conditional knockout mice show increased number of missteps and fewer normal steps compared with wildtype mice.
Exp Paradigm: Males only.
 Erasmus ladder test
 35 months
Miniature post synaptic current frequency: excitatory1
Decreased
Description: Shank2 conditional knockout mice show reduced frequency of mEPSPs compared to wild type control mice.
Exp Paradigm: Males and females tested.
 Whole-cell patch clamp: Purkinje cell and parallel fiber synapses
 2.7-3.3 weeks
Repetitive nose pokes1
Increased
Description: Shank2 conditional knockout mice show increased repetitive nose pokes compared to wild type controls.
Exp Paradigm: The frequency of nose-poking into a hole was counted manually in a blind manner. Males only.
 Hole-board test
 35 months
Anxiety1
Increased
Description: Shank2 conditional knockout mice show increased anxiety in the light-dark test, compared to wild type controls.
Exp Paradigm: Males only.
 Light-dark exploration test: Light-dark exploration test
 35 months
Targeted expression1
Decreased
Description: Shank2 conditional knockout mice show reduced expression of Shank2 protein in total cerebellar lysates or cerebellar Shank2 localized at the molecular cell layer of the cerebellar cortex, at parallel fiber excitatory synapses or in the dendrites of Purkinje cells as seen in wild type controls.
Exp Paradigm: Calbindin was used to label Purkinje cells. Males and females tested.- Western blot: Cerebellum
 Western blot: Cerebellum
 6-8 weeks, 1.9 months
Protein localization: synapse1
Decreased
Description: Shank2 conditional knockout mice show reductions in the levels of excitatory synaptic membrane proteins, including GluD2 and PSD93, compared to wild type control mice. Reduced synaptic levels of GluD2 are caused by reduction in total levels, whereas of PSD-93 is possibly due to reduced trafficking to the synapse.
Exp Paradigm: Crude Synaptosomal and total synaptic proteins were measured. Males and females tested.
 Western blot: cerebellum, synaptosomal
 2.7-3.3 weeks
Protein expression level evidence1
Decreased
Description: Shank2 conditional knockout mice show reductions in the levels of cerebellar excitatory synaptic membrane proteins, including GluD2 and PSD-93, and reduction of Homer and GluD2 but not PSD93 in total cerebellar lysates, compared to wild type control mice.
Exp Paradigm: Males and females tested.
 Western blot: cerebellum, excitatory synapse
 2.7-3.3 weeks
Targeted expression1
Decreased
Description: Shank2 conditional knockout mice show reduced expression of Shank2 protein in total cerebellar lysates or cerebellar Shank2 localized at the molecular cell layer of the cerebellar cortex, at parallel fiber excitatory synapses or in the dendrites of Purkinje cells as seen in wild type controls.
Exp Paradigm: Calbindin was used to label Purkinje cells. Males and females tested.-Immunofluorescence staining
 Immunofluorescence staining
 6-8 weeks, 1.9 months
Ultrasonic vocalization: Interaction induced: opposite sex stimulus1
 No Change
 Monitoring ultrasonic vocalizations
 Adult
Ultrasonic vocalization: Isolation induced1
 No Change
 Monitoring ultrasonic vocalizations
 P5-13
Anxiety1
 No Change
 Open field test
 35 months
Anxiety1
 No Change
 Elevated plus maze test
 35 months
Climbing1
 No Change
 Home cage behavior
 2 months
General locomotor activity: Ambulatory activity1
 No Change
 Home cage behavior
 2 months
Motor coordination and balance1
 No Change
 Accelerating rotarod test
 2 months
Miniature post synaptic current amplitude: excitatory1
 No Change
 Whole-cell patch clamp: Purkinje cell and parallel fiber synapses
 2.7-3.3 weeks
Synaptic plasticity: cerebellar LTD1
 No Change
 Whole-cell patch clamp: Purkinje cell and parallel fiber synapses
 2.7-3.3 weeks
Satiety response1
 No Change
 Food intake measurements
 2 months
Repetitive digging1
 No Change
 Marble-burying test
 35 months
Self grooming: perseveration1
 No Change
 Home cage behavior
 35 months
Vertical jumping or back flipping1
 No Change
 Home cage behavior
 35 months
Olfaction1
 No Change
 Olfactory habituation-dishabituation test
 23 months
Vision1
 No Change
 Cliff avoidance test
 23 months
Social approach1
 No Change
 Three-chamber social approach test
 23 months
Social interaction1
 No Change
 Reciprocal social interaction test
 2 months
Social memory1
 No Change
 Three-chamber social approach test
 23 months
 Not Reported: Circadian sleep/wake cycle, Developmental profile, Homeostasis, Immune response, Learning & memory, Maternal behavior, Neuroanatomy / Ultrastructure / Cytoarchitecture, Seizure

M_SHANK2_9_CKO_HM_PvalbN

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
General locomotor activity1
Increased
Description: Mutants show increased locomotor activity on the open field in the dark compared to controls.
 Open field test: darkness
 Adult
General locomotor activity1
Increased
Description: Mutants show increased locomotion in the home cage compared to controls.
 Open field test: home cage
 Adult
Self grooming: perseveration1
Increased
Description: Mutants show increased in self-grooming following introduction to a new home cage compared to controls.
 Novel cage test
 Adult
Electroencephalogram (EEG): signature of seizure/epilepsy1
Decreased
Description: Mutants show a delay in the progression to seizure stage after PTZ injection compared to controls, indicating mutants are more resistant to PTZ induced seizures. Mutants show an increase in latency to reach the first myoclonic seizure compared to controls
 Observation of chemically induced seizures: PTZ induced seizures
 Adult
Targeted expression1
Decreased
Description: Mutants show decrease in Shank2 expression in the brain, particularly in the cerebellum, compared to controls.
 Western blot
 3-4 months
Targeted expression1
Decreased
Description: Mutants show decrease in Shank2 protein in the cerebellum and the thalamic reticular nuclei of the thalamus, with no punctate expression in the neutropill regions, compared to controls.
 Immunohistochemistry
 Adult
Ultrasonic vocalization: Interaction induced: opposite sex stimulus1
 No Change
 Monitoring vocalizations
 Adult
Mortality/lethality1
 No Change
 Genotypic ratio of progeny from heterozygous parents
 Not reported
Size/growth1
 No Change
 General observations
 Not reported
Anxiety1
 No Change
 Open field test: darkness
 Adult
Anxiety1
 No Change
 Light-dark exploration test: Light-dark exploration test
 Adult
Anxiety1
 No Change
 Elevated plus maze test
 Adult
Cognitive flexibility1
 No Change
 Morris water maze test
 Adult
Cued or contextual fear conditioning: Memory of context1
 No Change
 Fear conditioning test
 Adult
Spatial reference memory1
 No Change
 Morris water maze test
 Adult
Spatial working memory1
 No Change
 Morris water maze test
 Adult
Targeted expression1
 No Change
 Western blot
 3-4 months
Motor coordination and balance1
 No Change
 Accelerating rotarod test
 Adult
Electroencephalogram (EEG) signature1
 No Change
 Electroencephalogram (EEG)
 Adult
Head bobbing1
 No Change
 Hole-board test
 
Repetitive digging1
 No Change
 Novel cage test
 Adult
Vertical jumping or back flipping1
 No Change
 Novel cage test
 Adult
Seizures1
 No Change
 General observations
 Adult
Huddling Behavior1
 No Change
 Reciprocal social interaction test
 Adult
Social approach1
 No Change
 Three-chamber social approach test
 Adult
Social interaction1
 No Change
 Reciprocal social interaction test
 Adult
 Not Reported: Circadian sleep/wake cycle, Homeostasis, Immune response, Maternal behavior, Neuroanatomy / Ultrastructure / Cytoarchitecture, Sensory

M_SHANK2_10_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission1
Decreased
Description: Mutants show decrease in NMDA/AMPA ratio at Schaffer collateral-CA1 pyramidal synapses at 3 weeks compared with controls.
 Whole-cell patch clamp: CA1
 3 weeks
Synaptic transmission: excitatory1
Decreased
Description: Mutants show decreased NMDAR mediated EPSCs at Schaffer collateral-CA1 pyramidal synapses at 3 weeks compared with controls.
 Whole-cell patch clamp: CA1
 3 weeks
Decay kinetics of miniature post synaptic currents1
 No Change
 Whole-cell patch clamp: CA1
 2, 3 weeks
Synaptic neuroreceptor ratio (NMDAR/AMPAR) dependent transmission1
 No Change
 Whole-cell patch clamp: CA1
 2 weeks
Synaptic transmission: excitatory1
 No Change
 Whole-cell patch clamp: CA1
 2, 3 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, Repetitive behavior, Seizure, Sensory, Social behavior

M_SHANK2_11_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Miniature post synaptic current amplitude: excitatory1
Decreased
Description: Mutants show decrease in NMDAR mEPSC amplitude at Schaffer collateral-CA1 pyramidal synapses at 3-4 weeks compared with controls.
 Whole-cell patch clamp: CA1
 3.4 weeks
Miniature post synaptic current frequency: excitatory1
 No Change
 Whole-cell patch clamp: CA1
 3.4 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, Repetitive behavior, Seizure, Sensory, Social behavior


Interactor Symbol Interactor Name Interactor Organism Entrez ID Uniprot ID Interaction Type Evidence Reference
DNM2 dynamin 2 1785 P50570 Y2H; IP/WB; GST
Okamoto PM , et al. 2001
PDE4D phosphodiesterase 4D, cAMP-specific 5144 Q08499 IP/WB; GST
Lee JH , et al. 2007
FMR1 fragile X mental retardation 1 14265 P35922 HITS-CLIP
Darnell JC , et al. 2011
GRID2 glutamate receptor, ionotropic, delta 2 14804 Q61625 Y2H; IP/WB; GST; Surface plasmon resonance (SPR)
Uemura T , et al. 2004
GRIP1 glutamate receptor interacting protein 1 74053 Q925T6 IP/WB
Uemura T , et al. 2004
Khdrbs3 KH domain containing, RNA binding, signal transduction associated 3 13992 Q9R226 RNA-Seq
Traunmller L , et al. 2016
ARHGEF7 Rho guanine nucleotide exchange factor (GEF7) 114559 O55043 Y2H; GST; IP/WB
Park E , et al. 2003
CFTR cystic fibrosis transmembrane conductance regulator homolog 12638 P26361 Y2H; IP/WB
Kim JY , et al. 2003
CTTN cortactin 60465 Q66HL2 Y2H; GST; IP/WB
Du Y , et al. 1998
DBNL Drebrin-like 13169 Q62418 GST; Far Western Blot
Qualmann B , et al. 2004
DLG4 discs, large homolog 4 (Drosophila) 29495 P31016 Y2H; IP/WB
Boeckers TM , et al. 1999
DLGAP1 discs, large (Drosophila) homolog-associated protein 1 65040 P97836 Y2H; GST; IP/WB
Naisbitt S , et al. 1999
DLGAP2 discs, large (Drosophila) homolog-associated protein 2 116681 P97837 Y2H
Boeckers TM , et al. 1999
DLGAP3 discs, large (Drosophila) homolog-associated protein 3 286923 P97838 Y2H
Boeckers TM , et al. 1999
DLGAP4 discs, large homolog-associated protein 4 (Drosophila) 286930 P97839 Y2H
Boeckers TM , et al. 1999
DYNLL1 dynein light chain LC8-type 1 58945 P63170 IP/WB
Naisbitt S , et al. 2000
DYNLL2 dynein light chain LC8-type 2 140734 Q78P75 IP/WB
Naisbitt S , et al. 2000
HOMER1 homer homolog 1 (Drosophila) 29456 Q9Z214 GST; IP/WB
Hwang JI , et al. 2005
ITPR3 inositol 1,4,5-triphosphate receptor, type 3 25679 Q63269 IP/WB
Hwang JI , et al. 2005
LPHN1 latrophilin 1 65096 O88917 Y2H; Far Western Blot; IP/WB
Kreienkamp HJ , et al. 2000
LRRC7 leucine rich repeat containing 7 117284 P70587 IP/WB; GST
Quitsch A , et al. 2005
MYO5A myosin VA 25017 Q9QYF3 IP/WB
Naisbitt S , et al. 2000
PLCB3 phospholipase C, beta 3 29322 Q99JE6 Y2H; GST; IP/WB
Hwang JI , et al. 2005
SLC4A7 solute carrier family 4, sodium bicarbonate cotransporter, member 7 117955 Q9R1N3 Y2H
Kim JY , et al. 2003
SLC9A3 solute carrier family 9 (sodium/hydrogen exchanger), member 3 24784 P26433 Y2H; IP/WB; Surface plasmon resonance (SPR)
Han W , et al. 2005
SSTR2 somatostatin receptor 2 54305 P30680 Y2H; Far Western Blot; IP/WB
Zitzer H , et al. 1999
LZTS2 leucine zipper, putative tumor suppressor 2 495421 Q5U4W1 IP/WB
Gessert S , et al. 2011

HELP
Copyright © 2017 MindSpec, Inc.