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Relevance to Autism

Studies have found rare single gene variations in the NLGN3 gene in autism. However, other studies claimed to find no rare variations in the NLGN3 gene in autism patients, although one of these found several silent variations. One study (Ylisaukko-oja et al., 2005) found a genetic association between an NLGN3 variant and autism in a sample of Finnish autism families, and another study (Yu et al., 2011) found a genetic association between an NLGN3 variant and autism in the Chinese Han population. This gene was identified by TADA (transmission and de novo association) analysis of a combined dataset from the Simons Simplex Collection (SSC) and the Autism Sequencing Consortium (ASC) as a gene strongly enriched for variants likely to affect ASD risk with a false discovery rate (FDR) of <0.1 (Sanders et al., 2015); among the variants identified in this gene was one de novo loss-of-function (LoF) variant.

Molecular Function

This gene encodes a member of a family of neuronal cell-adhesion proteins located at the postsynaptic side of the synapse. Members of this family may act as splice site-specific ligands for beta-neurexins and may be involved in the formation and remodeling of central nervous system synapses.

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism.
ASD
Positive Association
A sex-specific association of common variants of neuroligin genes (NLGN3 and NLGN4X) with autism spectrum disorders in a Chinese Han cohort.
ASD
Positive Association
Analysis of four neuroligin genes as candidates for autism.
ASD
Negative Association
Absence of coding mutations in the X-linked genes neuroligin 3 and neuroligin 4 in individuals with autism from the IMGSAC collection.
ASD
Negative Association
NLGN3/NLGN4 gene mutations are not responsible for autism in the Quebec population.
ASD
Negative Association
Mutation screening of X-chromosomal neuroligin genes: no mutations in 196 autism probands.
ASD
Negative Association
Not all neuroligin 3 and 4X missense variants lead to significant functional inactivation.
ASD
Negative Association
Variations analysis of NLGN3 and NLGN4X gene in Chinese autism patients.
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
No evidence for involvement of genetic variants in the X-linked neuroligin genes NLGN3 and NLGN4X in probands with autism spectrum disorder on high...
ASD
Support
Identification of rare X-linked neuroligin variants by massively parallel sequencing in males with autism spectrum disorder.
ASD
Support
Large-scale discovery of novel genetic causes of developmental disorders.
Specific learning disability
Support
Identification of Four Novel Synonymous Substitutions in the X-Linked Genes Neuroligin 3 and Neuroligin 4X in Japanese Patients with Autistic Spect...
ASD
Support
The contribution of de novo coding mutations to autism spectrum disorder
ASD
Support
An Autism-Associated Neuroligin-3 Mutation Affects Developmental Synapse Elimination in the Cerebellum
ASD
Support
Efficient strategy for the molecular diagnosis of intellectual disability using targeted high-throughput sequencing.
ID
Support
Abnormal Social Interactions in a Drosophila Mutant of an Autism Candidate Gene: Neuroligin 3
Support
Excess of rare novel loss-of-function variants in synaptic genes in schizophrenia and autism spectrum disorders.
ASD, SCZ
Support
Neuroligin 3 Regulates Dendritic Outgrowth by Modulating Akt/mTOR Signaling.
Support
Detection of clinically relevant genetic variants in autism spectrum disorder by whole-genome sequencing.
ASD
Support
Novel mutations in NLGN3 causing autism spectrum disorder and cognitive impairment.
ASD or autistic behavior, ID
Support
Using whole-exome sequencing to identify inherited causes of autism.
ASD
Support
Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder
ASD
Recent Recommendation
Expression patterns of neurexin-1 and neuroligins in brain and retina of the chick embryo: Neuroligin-3 is absent in retina.
Recent Recommendation
Autism-associated neuroligin-3 mutations commonly disrupt tonic endocannabinoid signaling.
Recent Recommendation
Modulation of excitation on parvalbumin interneurons by neuroligin-3 regulates the hippocampal network.
Recent Recommendation
The Arg473Cys-neuroligin-1 mutation modulates NMDA mediated synaptic transmission and receptor distribution in hippocampal neurons.
Recent Recommendation
Autism-linked neuroligin-3 R451C mutation differentially alters hippocampal and cortical synaptic function.
Recent Recommendation
Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci.
ASD
Recent Recommendation
Neuroligin trafficking deficiencies arising from mutations in the alpha/beta-hydrolase fold protein family.
Recent Recommendation
Integrated systems analysis reveals a molecular network underlying autism spectrum disorders.
ASD
Recent Recommendation
Differential expression of neuroligin genes in the nervous system of zebrafish.
Recent Recommendation
Autism-associated neuroligin-3 mutations commonly impair striatal circuits to boost repetitive behaviors.
Recent Recommendation
A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice.
Recent Recommendation
Autism-related neuroligin-3 mutation alters social behavior and spatial learning.
Recent Recommendation
A mutation linked with autism reveals a common mechanism of endoplasmic reticulum retention for the alpha,beta-hydrolase fold protein family.
Recent Recommendation
Developmental regulation of GABAergic signalling in the hippocampus of neuroligin 3 R451C knock-in mice: an animal model of Autism.

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN171R001 
 missense_variant 
 c.1351C>T 
 p.Arg451Ter 
 Familial 
 Maternal 
 Multiplex 
 GEN171R002 
 synonymous_variant 
 A>G 
 p.(=) 
  
  
  
 GEN171R003 
 synonymous_variant 
 C>G 
 p.(=) 
  
  
  
 GEN171R004 
 synonymous_variant 
 G>A 
 p.(=) 
  
  
  
 GEN171R005 
 synonymous_variant 
 G>A 
 p.(=) 
  
  
  
 GEN171R006 
 synonymous_variant 
 G>A 
 p.(=) 
  
  
  
 GEN171R007 
 synonymous_variant 
 G>A 
 p.(=) 
  
  
  
 GEN171R008 
 synonymous_variant 
 G>A 
 p.(=) 
  
  
  
 GEN171R009 
 missense_variant 
 c.2189G>A 
 p.Thr632Ala 
 Familial 
 Maternal 
 Multiplex 
 GEN171R010 
 synonymous_variant 
 c.222C>T 
 p.Tyr74= 
 Familial 
  
 Multiplex 
 GEN171R011 
 intron_variant 
 c.607+47G>C 
  
 Unknown 
  
 Unknown 
 GEN171R012 
 synonymous_variant 
 c.1698G>A 
 p.Lys566= 
 Unknown 
  
 Unknown 
 GEN171R013 
 intron_variant 
  
  
 Unknown 
  
 Multiplex 
 GEN171R014 
 intron_variant 
  
  
 Unknown 
  
 Multiplex 
 GEN171R015 
 intron_variant 
  
  
 Unknown 
  
 Multiplex 
 GEN171R016 
 intron_variant 
  
  
 Unknown 
  
 Multiplex 
 GEN171R017 
 3_prime_UTR_variant 
  
  
 Familial 
 Maternal 
 Multiplex 
 GEN171R018 
 missense_variant 
 c.962T>C 
 p.Val321Ala 
 Familial 
 Maternal 
 Simplex 
 GEN171R019 
 missense_variant 
 c.916G>A 
 p.Val306Met 
 Familial 
 Maternal 
 Simplex 
 GEN171R020 
 frameshift_variant 
 c.311del 
 p.Pro104GlnfsTer41 
 Unknown 
  
 Unknown 
 GEN171R021 
 missense_variant 
 c.1276G>A 
 p.Gly426Ser 
 De novo 
 NA 
 Simplex 
 GEN171R022 
 missense_variant 
 c.1954A>G 
 p.Thr652Ala 
 Unknown 
  
 Unknown 
 GEN171R023 
 stop_gained 
 c.1328G>A 
 p.Trp443Ter 
 Familial 
 Maternal 
 Simplex 
 GEN171R024 
 missense_variant 
 c.1729C>T 
 p.Arg577Trp 
 Familial 
 Maternal 
 Extended multiplex 
 GEN171R025 
 missense_variant 
 c.583C>T 
 p.Arg195Trp 
 De novo 
 NA 
 Simplex 
 GEN171R026 
 frameshift_variant 
 c.1228dup 
 p.Leu410ProfsTer16 
 Familial 
 Maternal 
 Simplex 
 GEN171R027 
 frameshift_variant 
 c.1228dup 
 p.Leu410ProfsTer16 
 Familial 
 Maternal 
 Simplex 
 GEN171R028 
 missense_variant 
 c.1480C>T 
 p.Pro494Ser 
 Familial 
 Maternal 
 Multiplex 

Common

Variant ID
Polymorphism
SNP ID
Allele Change
Residue Change
Population Origin
Population Stage
Author, Year
 GEN171C001 
 intron_variant 
 rs11795613 
 c.-200-72A>G;c.-272A>G;c.-38-585A>G;c.47-72A>G;c.-116-72A>G 
 G/A 
 Chinese Han 
 Discovery 
 GEN171C002 
 intron_variant 
 rs4844285 
 c.457+2188G>A;c.517+1489G>A;c.106+2188G>A;c.328+1489G>A;c.166+1489G>A 
 A to G 
 Chinese Han 
 Discovery 
 GEN171C003 
 intron_variant 
 rs4844286 
 c.458-3490T>G;c.458-1753T>G;c.518-1753T>G;c.107-1753T>G;c.329-1753T>G;c.167-1753T>G 
 G to T 
 Chinese Han 
 Discovery 
 GEN171C004 
 intron_variant 
 rs5981079 
 c.458-2809T>C;c.458-1072T>C;c.518-1072T>C;c.107-1072T>C;c.329-1072T>C;c.167-1072T>C 
 C to T 
 Chinese Han 
 Discovery 
 GEN171C005 
 intron_variant 
 rs7051529 
 c.458-860A>G;c.517+818A>G;c.577+818A>G;c.166+818A>G;c.388+818A>G;c.226+818A>G 
 G/A 
 Chinese Han 
 Discovery 
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
X
Deletion
 1
 
X
Duplication
 1
 
X
Deletion
 1
 
X
Deletion-Duplication
 18
 
X
Deletion
 2
 
X
Duplication
 1
 
X
Duplication
 2
 
X
Duplication
 1
 
X
Deletion-Duplication
 14
 
X
Duplication
 1
 

Model Summary

Mutant mice display impaired social interactions; increase in inhibitory synaptic transmission.

References

Type
Title
Author, Year
Primary
A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice.
Additional
Neuroligin-3-deficient mice: model of a monogenic heritable form of autism with an olfactory deficit.
Additional
Minimal aberrant behavioral phenotypes of neuroligin-3 R451C knockin mice.
Additional
Autism-linked neuroligin-3 R451C mutation differentially alters hippocampal and cortical synaptic function.
Additional
Shared synaptic pathophysiology in syndromic and nonsyndromic rodent models of autism.
Additional
Developmental regulation of GABAergic signalling in the hippocampus of neuroligin 3 R451C knock-in mice: an animal model of Autism.
Additional
Autism-associated neuroligin-3 mutations commonly impair striatal circuits to boost repetitive behaviors.
Additional
Enhanced synapse remodelling as a common phenotype in mouse models of autism.
Additional
Neuroligins Sculpt Cerebellar Purkinje-Cell Circuits by Differential Control of Distinct Classes of Synapses.
Additional
Neuroligin 3 R451C mutation alters electroencephalography spectral activity in an animal model of autism spectrum disorders.
Additional
Male and Female Mice Lacking Neuroligin-3 Modify the Behavior of Their Wild-Type Littermates.
Additional
The neurobiological bases of autism spectrum disorders: the R451C-neuroligin 3 mutation hampers the expression of long-term synaptic depression in ...
Additional
Genetic background effects in Neuroligin-3 mutant mice: Minimal behavioral abnormalities on C57 background.
Additional
Gamma Oscillation Dysfunction in mPFC Leads to Social Deficits in Neuroligin 3 R451C Knockin Mice.
Additional
Role of VTA dopamine neurons and neuroligin 3 in sociability traits related to nonfamiliar conspecific interaction.
Additional
UPR activation specifically modulates glutamate neurotransmission in the cerebellum of a mouse model of autism.
Additional
Striatal Inhibition of MeCP2 or TSC1 Produces Sociability Deficits and Repetitive Behaviors.
Additional
Gastrointestinal dysfunction in patients and mice expressing the autism-associated R451C mutation in neuroligin-3.
Additional
Rescue of oxytocin response and social behaviour in a mouse model of autism
Additional
An altered glial phenotype in the NL3 R451C mouse model of autism
Additional
Learning and reaction times in mouse touchscreen tests are differentially impacted by mutations in genes encoding postsynaptic interacting proteins SYNGAP1, NLGN3, DLGAP1, DLGAP2 and SHANK2
Additional
Canonical versus non-canonical transsynaptic signaling of neuroligin 3 tunes development of sociality in mice

M_NLGN3_1_KI_R451C

Model Type: Genetic
Model Genotype: Hemizygous
Mutation: Exon 7 carrying coding mutation (R451C) replaced the wild type exon 7 using a neo cassette as a selectable marker and flanked by loxP sites.
Allele Type: ASD LOF mutation
Strain of Origin: (129X1/SvJ x 129S1/Sv)F1-Kitl+
Genetic Background: C57BL6J * 129S2
ES Cell Line: R1
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_NLGN3_2_KO

Model Type: Genetic
Model Genotype: Hemizygous
Mutation: Exons 2 and 3 flanked by loxP sites, then removed by cre-mediated recombination.
Allele Type: Knockout
Strain of Origin: (129X1/SvJ x 129S1/Sv)F1-Kitl+
Genetic Background: 129S1/Sv * 129X1/SvJ * C57BL/6
ES Cell Line: R1
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_NLGN3_4_KO

Model Type: Genetic
Model Genotype: Hemizygous
Mutation: Exon sequence covering the translational start site and 574 bp of 5' coding sequence targeted for deletion by homologous recombination.
Allele Type: Knockout
Strain of Origin: Not Specified
Genetic Background: C57BL/6NCrl
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: 16982420

M_NLGN3_3_KI_R451C

Model Type: Genetic
Model Genotype: Hemizygous, Homozygous
Mutation: A BAC targeting vector with the mutation of CGT (arginine 451) to TGC (cysteine 451) in exon 7 replaced the wild-type sequence.
Allele Type: ASD LOF mutation
Strain of Origin: Not Specified
Genetic Background: C57BL/6
ES Cell Line: R1
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_NLGN3_16_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Mutant mice carrying a Neo-STOP-tetO cassette inserted after the transcriptional start site of Nlgn3 which results in a complete loss of NL3 expression. Doxycycline (100microg/ml) was added to the drinking water during breeding and after weaning of pups.
Allele Type: Knockout
Strain of Origin: Not Specified
Genetic Background: C57BL/6
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_NLGN3_10_CKO_HM

Model Type: Genetic
Model Genotype: Hemizygous
Mutation: Conditional deletion of exons 2 - 3 of Nlgn3 using D1-cre, in neurons expressing dopamine receptor Drd1a, authors specifically looked at D1a expressing medium spiny neurons in the striatum
Allele Type: Conditional loss-of-function
Strain of Origin: (129X1/SvJ x 129S1/Sv)F1-Kitl+
Genetic Background: C57BL/6J
ES Cell Line: R1
Mutant ES Cell Line: Not Specified
Model Source:

M_NLGN3_11_CKO_HM

Model Type: Genetic
Model Genotype: Hemizygous
Mutation: Conditional deletion of exons 2 - 3 of Nlgn3 using A2a-cre, in medium spiny neurons of striatal indirect pathway (striatopallidal) expressing adenosine-2a receptor, that are also known to express dopamine receptor 2 (Drd2)
Allele Type: Conditional loss-of-function
Strain of Origin: (129X1/SvJ x 129S1/Sv)F1-Kitl+
Genetic Background: C57BL/6J
ES Cell Line: R1
Mutant ES Cell Line: Not Specified
Model Source:

M_NLGN3_12_KI_R451C_D1-CRE

Model Type: Genetic
Model Genotype: Hemizygous
Mutation: Exon 7 carrying coding mutation (R451C) replaced the wild type exon 7 using a neo cassette as a selectable marker and flanked by loxP sites, D1-Cre transgene.
Allele Type: ASD LOF mutation
Strain of Origin: (129X1/SvJ x 129S1/Sv)F1-Kitl+
Genetic Background: C57BL/6J
ES Cell Line: R1
Mutant ES Cell Line: Not Specified
Model Source:

M_NLGN3_13_CKO_HM_DS

Model Type: Genetic
Model Genotype: Hemizygous
Mutation: Conditional deletion of exons 2 - 3 of Nlgn3 using AAV-Cre transgene under the synapsin promoter, injected into the dorsal striatum in 4 week old mice
Allele Type: Conditional loss-of-function
Strain of Origin: (129X1/SvJ x 129S1/Sv)F1-Kitl+
Genetic Background: C57BL/6J
ES Cell Line: R1
Mutant ES Cell Line: Not Specified
Model Source:

M_NLGN3_14_CKO_HM_NAC

Model Type: Genetic
Model Genotype: Hemizygous
Mutation: Conditional deletion of exons 2 - 3 of Nlgn3 using AAV-Cre transgene under the synapsin promoter, injected into the nucleus accumbens in 4 week old mice
Allele Type: Conditional loss-of-function
Strain of Origin: (129X1/SvJ x 129S1/Sv)F1-Kitl+
Genetic Background: C57BL/6J
ES Cell Line: R1
Mutant ES Cell Line: Not Specified
Model Source:

M_NLGN3_5_KO

Model Type: Genetic
Model Genotype: Hemizygous
Mutation: Exons 2 and 3 flanked by loxP sites, then removed by cre-mediated recombination.
Allele Type: Knockout
Strain of Origin: (129X1/SvJ x 129S1/Sv)F1-Kitl+
Genetic Background: C57BL/6J
ES Cell Line: R1
Mutant ES Cell Line: Not Specified
Model Source:

M_NLGN3_6_KI_R451C

Model Type: Genetic
Model Genotype: Hemizygous
Mutation: Exon 7 carrying coding mutation (R451C) replaced the wild type exon 7 using a neo cassette as a selectable marker and flanked by loxP sites.
Allele Type: ASD LOF mutation
Strain of Origin: (129X1/SvJ x 129S1/Sv)F1-Kitl+
Genetic Background: C57BL/6J
ES Cell Line: R1
Mutant ES Cell Line: Not Specified
Model Source:

M_NLGN3_7_CKO_NESTIN-CRE

Model Type: Genetic
Model Genotype: Hemizygous
Mutation: Conditional deletion of exons 2-3 of Nlgn3 using Nestin-cre, in neuronal, glial and other cell types in the central and peripheral nervous system
Allele Type: Conditional loss-of-function
Strain of Origin: (129X1/SvJ x 129S1/Sv)F1-Kitl+
Genetic Background: C57BL/6J
ES Cell Line: R1
Mutant ES Cell Line: Not Specified
Model Source:

M_NLGN3_8_CKO_HM_PURKINJEN

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Conditional deletion of exons 2-3 of Nlgn3 using L7-cre in Purkinje cells of the cerebellum
Allele Type: Conditional knockout
Strain of Origin: Not Specified
Genetic Background: C57BL/6*129Sv/CD1
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Jackson Labs

M_NLGN3_8_CKO_L7-CRE

Model Type: Genetic
Model Genotype: Hemizygous
Mutation: Exons 2 and 3 flanked by loxP sites, L7-Cre transgene.
Allele Type: Conditional knockout
Strain of Origin: (129X1/SvJ x 129S1/Sv)F1-Kitl+
Genetic Background: C57BL/6J
ES Cell Line: R1
Mutant ES Cell Line: Not Specified
Model Source:

M_NLGN3_9_CKO_HM_PVALBN

Model Type: Genetic
Model Genotype: Hemizygous
Mutation: Conditional deletion of exons 2-3 of Nlgn3 using Pvalb-Cre, in parvalbumin expressing interneurons
Allele Type: Conditional loss-of-function
Strain of Origin: (129X1/SvJ x 129S1/Sv)F1-Kitl+
Genetic Background: C57BL/6J
ES Cell Line: R1
Mutant ES Cell Line: Not Specified
Model Source:

M_NLGN3_1_KI_R451C_GEPH-GFP

Model Type: Genetic
Model Genotype: Hemizygous
Mutation: The progenitor cells for layer 2/3 neurons in the somatosensory cortex and anterior frontal cortex of NLGN3_1_KI_R451C mice were transfected using in utero electroporation to label excitatory synapses. E15.5 timed pregnant mice were deeply anaesthetized, their uterine horns were exposed and approximately 1ul of DNA mixture, containing DsRed2 plasmid (1ug/ul) and Gephyrin-GFP plasmid (1-2ug/ul), was pressure injected into the lateral ventricle of each embryo through a micropipette. Electric pulses were passed through the head of each embryo using two tweezer type electrodes for electroporation.
Allele Type: ASD LOF mutation
Strain of Origin: (129X1/SvJ x 129S1/Sv)F1-Kitl+
Genetic Background: 129S1/Sv * 129X1/SvJ * C57BL/6
ES Cell Line: R1
Mutant ES Cell Line:
Model Source:

M_NLGN3_1_KI_R451C_PSD95-GFP

Model Type: Genetic
Model Genotype: Hemizygous
Mutation: The progenitor cells for layer 2/3 neurons in the somatosensory cortex and anterior frontal cortex of NLGN3_1_KI_R451C mice were transfected using in utero electroporation to label excitatory synapses. E15.5 timed pregnant mice were deeply anaesthetized, their uterine horns were exposed and approximately 1ul of DNA mixture, containing DsRed2 plasmid (1ug/ul) and PSD-95-GFP plasmid (1-2ug/ul), was pressure injected into the lateral ventricle of each embryo through a micropipette. Electric pulses were passed through the head of each embryo using two tweezer type electrodes for electroporation.
Allele Type: ASD LOF mutation
Strain of Origin: (129X1/SvJ x 129S1/Sv)F1-Kitl+
Genetic Background: 129S1/Sv * 129X1/SvJ * C57BL/6
ES Cell Line: R1
Mutant ES Cell Line:
Model Source:

M_NLGN3_19_KO_HE

Model Type: Genetic
Model Genotype: Hemizygous
Mutation: Male Nlgn3 (y/-) mice from mixed genotype housing (MGH), that is co-housed with wild-type Nlgn3 (y/+) littermates. Control mice were Nlgn3 (y/+) mice littermates or from SGH (single genotype housing) as applicable. Nlgn3 null allele contains a stop cassette flanked by loxP sites in the promoter region and lack Nlgn3 expression (Tanaka KF, et al., 2010; PMID 20163789).
Allele Type: Knockout
Strain of Origin: Not Specified
Genetic Background: C57BL/6
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source:

M_NLGN3_20_KO_HE

Model Type: Genetic
Model Genotype: Hemizygous
Mutation: Male Nlgn3 (y/-) mice from single genotype housing (SGH). Control mice were Nlgn3 (y/+) mice from SGH. Nlgn3 null allele contains a stop cassette flanked by loxP sites in the promoter region and lack Nlgn3 expression (Tanaka KF, et al., 2010; PMID 20163789).
Allele Type: Knockout
Strain of Origin: Not Specified
Genetic Background: C57BL/6
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source:

M_NLGN3_22_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Female Nlgn3 (-/-) mice in single genotype housing (SGH) were generated by crossing Nlgn3 (-/-) dams with Nlgn3 (y/-) sires. Nlgn3 null allele contains a stop cassette flanked by loxP sites in the promoter region and lack Nlgn3 expression (Tanaka KF, et al., 2010; PMID 20163789).
Allele Type: Knockout
Strain of Origin: Not Specified
Genetic Background: C57BL/6
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source:

M_NLGN3_23_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Female Nlgn3 (-/-) mice housed with heterozygous female littermates (H-KO) were generated by crossing Nlgn3 (+/-) dams with Nlgn3 (y/-) sires. Nlgn3 null allele contains a stop cassette flanked by loxP sites in the promoter region and lack Nlgn3 expression (Tanaka KF, et al., 2010; PMID 20163789).
Allele Type: Knockout
Strain of Origin: Not Specified
Genetic Background: C57BL/6
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source:

M_NLGN3_24_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Female Nlgn3 (+/-) mice housed with null female littermates (H-KO) were generated by crossing Nlgn3 (+/-) dams with Nlgn3 (y/-) sires. Nlgn3 null allele contains a stop cassette flanked by loxP sites in the promoter region and lack Nlgn3 expression (Tanaka KF, et al., 2010; PMID 20163789).
Allele Type: Knockout
Strain of Origin: Not Specified
Genetic Background: C57BL/6
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source:

M_NLGN3_25_KO_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Female Nlgn3 (+/-) mice housed with wildtype female littermates (H-WT) were generated by crossing Nlgn3 (+/-) dams with Nlgn3 (y/+) sires. Nlgn3 null allele contains a stop cassette flanked by loxP sites in the promoter region and lack Nlgn3 expression (Tanaka KF, et al., 2010; PMID 20163789).
Allele Type: Knockout
Strain of Origin: Not Specified
Genetic Background: C57BL/6
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source:

M_NLGN3_26_KI_R451C

Model Type: Genetic
Model Genotype: Hemizygous
Mutation: Mice harbor the mutation of CGT (arginine 451) to TGC (cysteine 451) in exon 7.
Allele Type: ASD LOF mutation
Strain of Origin: (129X1/SvJ x 129S1/Sv)F1-Kitl+
Genetic Background: B6*129
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Sudhof laboratory (PMID 17823315 )

M_NLGN3_21_KI_R451C

Model Type: Genetic
Model Genotype: Hemizygous
Mutation: Exon 7 was replaced with an exon 7 carrying an arginine to cysteine amino acid substitution at position 451 (R451C). A neo cassette was used as a selectable marker. KI mice were crossed with G42 mice (G42: CB6-Tg(Gad1-EGFP)G42Zjh/J) to tag Gad1 positive interneurons. .
Allele Type: ASD LOF mutation
Strain of Origin: Not Specified
Genetic Background: C57BL/6J
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: The Jackson Laboratory; Chadman et al., 2008 PMID 19360662

M_NLGN3_27_KD

Model Type: Genetic
Model Genotype: Wild type
Mutation: For NL3 knockdown of 8-week-old male WT mice, pAAV-CMV-mCherry-shRNA-Nlgn3 (ObioTechnology, Shanghai, China) containing AAV-virus was injected (600 nL/hemisphere) into the mPFC.
Allele Type: Knockdown
Strain of Origin: Not Specified
Genetic Background: Not Specified
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: The Jackson Laboratory

M_NLGN3_28_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Nlgn3 knockout mice were generated using the Flexible Accelerated STOP Tetracycline Operator (tetO)-knockin (FAST) technology to insert a construct containing a loxP site, FRT site, neo cassette, STOP, FRT site, tetracycline operator (tetO) and loxP site
Allele Type: Knockout
Strain of Origin: 129S6/SvEvTac
Genetic Background: C57BL/6J
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: 20163789

M_NLGN3_29_KD

Model Type: Genetic
Model Genotype: Other
Mutation: Injections of purified AAV2-DIO-miRNlgn3-GFP, AAV2-Synaptophysin-GFPand AAV2-DIO-miR-GFP were done at P5P6 DAT-Cre mice for developmental knockdown. The virus was incubated for 34 weeks prior to testing. (AAV2-DIO-miRNlgn3in DAT-Cre mice: VTA::DA^NL3KD)
Allele Type: Knockdown
Strain of Origin:
Genetic Background: C57BL/6J
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: 30093665

M_NLGN3_30_KD

Model Type: Genetic
Model Genotype: Other
Mutation: Injections of purified AAV2-DIO-miRNlgn3-GFP, AAV2-Synaptophysin-GFPand AAV2-DIO-miR-GFP were done at 47 weeks for adult knockdown. The virus was incubated for 34 weeks prior to testing.
Allele Type: Knockdown
Strain of Origin:
Genetic Background: C57BL/6J
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: 30093665

M_NLGN3_31_KI_HE_R451C

Model Type: Genetic
Model Genotype: Hemizygous
Mutation: B6;129-Nlgn3tm1Sud/J knock-in mice (R451C). Mice carry an R451C mutation in exon 7 of the Nlgn3 gene.
Allele Type: Knockin
Strain of Origin: Not reported
Genetic Background: C57Bl/6*129sV
ES Cell Line: Not reported
Mutant ES Cell Line: Not reported
Model Source: gift from Dr. Andrea Barberis (Italian Institute of Technology, Genoa)

M_NLGN3_18_KD

Model Type: Genetic
Model Genotype: Wildtype
Mutation: Seven-week-old wildtype C57BL/6 male mice were injected with Nlgn3-siRNA (1392209,NM_172932.1), bilaterally in the dorsal striatum using a stereotaxic apparatus, resulting in a reduction of Nlgn3 transcript levels to about 0.6 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_NLGN3_32_KO_HE

Model Type: Genetic LOF
Model Genotype: Hemizygous
Mutation: Exon sequence covering the translational start site and 574 bp of 5' coding sequence targeted for deletion by homologous recombination (existing construct as in m_nlgn3_4_ko but on a different background)
Allele Type: Knockout
Strain of Origin:
Genetic Background: C57BL/6J
ES Cell Line: Not specified
Mutant ES Cell Line: Not specified
Model Source: Prof. Nils Brose (Max Planck Institute for Experimental Medicine) #16982420

M_NLGN3_32_KI_HE_HSE-AAA

Model Type: Genetic LOF
Model Genotype: Hemizygous
Mutation: Knock-in mutant mice with the HSE/AAA mutation were generated using CRISPR/Cas9 genome editing. The mutations consists of H279A S280A and E281A triple mutation (HSE/AAA) altering His279, Ser380, and Glu281, which comprise a near the interaction site for PTPĪ“ and NRXNs.
Allele Type: knockin
Strain of Origin: C57Bl/6
Genetic Background: C57Bl/6
ES Cell Line: NA
Mutant ES Cell Line: NA
Model Source: 33758193

M_NLGN3_33_KI_HE_MF-AA

Model Type: Genetic LOF
Model Genotype: Hemizygous
Mutation: Knock-in mutant mice with the MF/AA mutation were generated using CRISPR/Cas9 genome editing. MF/AA consists of M614A and F615A double mutations which disturbs the interface between PTPĪ“ Ig2 and the C-terminal tail of NLGN3 ECD without any effect on the interaction with NRXNs.
Allele Type: knockin
Strain of Origin: C57Bl/6
Genetic Background: C57Bl/6
ES Cell Line: NA
Mutant ES Cell Line: NA
Model Source: 33758193

M_NLGN3_34_CKO_HM

Model Type: Genetic LOF
Model Genotype: Hemizygous
Mutation: Knockout mouse model lacking exon 7 through Cre deletion. Exon 7 encodes a half of the extracellular domain, and skipping of this exon is predicted to lead to a frame shift and a premature stop codon. Nlgn3 exon 7-deleted mice were generated by crossing heterozygous female XX^fR/C mice, which carry floxed exon 7 with a point mutation corresponding to the human NLGN3 R451C, with nestin-Cre transgenic male mice (+/nestin-cre) carrying the cre recombinase gene under the control of the rat nestin promoter and enhancer.
Allele Type: knockout
Strain of Origin: C57Bl/6
Genetic Background: C57Bl/6
ES Cell Line: NA
Mutant ES Cell Line: NA
Model Source: 33758193

M_NLGN3_1_KI_R451C

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Motor coordination and balance4
Increased
Description: Normal initial coordination with increased learning rate, compared to male littermate controls
Exp Paradigm: Accelerating rotarod, nine trials 4 to 40 rpm in 300 s
 Accelerating rotarod test
 6 weeks
Hippocampal morphology2
Increased
Description: Increased dendritic branching of pyramidal neurons in stratum radiatum, compared to wild type, but no change in stratum lacunosum or stratum moleculare
Exp Paradigm: Sholl analysis
 Sholl analysis
 Unreported
Synaptic morphology2
Decreased
Description: Decreased spine area, bouton area and number of vesicles per bouton, compared to wild type
Exp Paradigm: Electron microscopy analysis
 Electron microscopy
 Unreported
Synapse density: inhibitory1
Increased
Description: Increased density of inhibitory synapse protein markers: vgat and gephyrin
Exp Paradigm: Immunohistochemistry; fluorescence microscopy
 Immunohistochemistry
 3 months
Neuronal number: enteric neurons5
Increased
Description: Mutants show increase in the number of myenteric neurons (hu cells) and increase in nnos positive inhibitory enteric neurons per ganglion in the proximal jejunum.
Exp Paradigm: Proximal jejunum
 Immunofluorescence staining
 8-12 weeks
Spontaneous post synaptic events3
Increased
Description: Increased frequency of spontaneous mini gaba postsynaptic current events but no change in amplitude, compared to wild type
Exp Paradigm: Whole-cell voltage-clamp recordings
 Whole-cell patch clamp
 P11-p15
Synaptic plasticity: hippocampal ltp2
Increased
Description: Increased fepsp slope 55-60 minutes after tetanic stimulation, compared to wild type
Exp Paradigm: Field potential recordings; long-term potentiation three 100-hz, 1-s stimuli
 Field potential recordings
 Unreported
Intrinsic bursting events or spikes3
Increased
Description: Increased spontaneous giant depolarizing potentials indicated by shorter cumulative inter-event-interval and higher cumulative probability in ca3 region of hippocampus, compared to wild type
Exp Paradigm: Whole-cell voltage-clamp recordings from ca3 region of hippocampus
 Whole-cell patch clamp
 P4-p9
Spontaneous post synaptic events: excitatory currents3
Increased
Description: Increased frequency of spontaneous mini ampa postsynaptic current events but no change in amplitude, compared to wild type
Exp Paradigm: Whole-cell voltage-clamp recordings
 Whole-cell patch clamp
 4-5 weeks
Synaptic transmission: inhibitory3
Abnormal
Description: Faster decay time of miniature gabaergic events, but no change in rise time, compared to wild type
Exp Paradigm: Whole-cell voltage-clamp recordings of mgpscs with gabaa competitive blocker
 Whole-cell patch clamp
 P9-p11
Spontaneous post synaptic events3
Increased
Description: Increased frequency of spontaneous mini gaba postsynaptic current events but no change in amplitude, compared to wild type
Exp Paradigm: Whole-cell voltage-clamp recordings
 Whole-cell patch clamp
 4-5 weeks
Synaptic neuroreceptor ratio (nmdar/ampar) dependent transmission2
Increased
Description: Increased ratio of nmda/ampa-mediated transmission in hippocampus, compared to wild type
Exp Paradigm: Whole cell patch-clamp recordings
 Whole-cell patch clamp
 Unreported
Spontaneous post synaptic events: excitatory currents2
Increased
Description: Increased frequency of spontaneous mepscs in hippocampus, compared to wild type
Exp Paradigm: Whole cell patch-clamp recordings
 Whole-cell patch clamp
 Unreported
Synaptic transmission: excitatory2
Abnormal
Description: Increased sensitivity to ifenprodil, nr1/nr2b heterotetrameric-selective antagonist, compared to wild type
Exp Paradigm: Field potential recordings
 Field potential recordings
 Unreported
Neurotransmitter release3
Increased
Description: Increased gaba transient in synaptic cleft indicated by decreased reduction of mgpscs amplitude after bath application of tpmpa, compared to wild type
Exp Paradigm: Whole-cell voltage-clamp recordings of mgpscs with gabaa competitive blocker
 Whole-cell patch clamp
 P11-p15
Spontaneous post synaptic events: inhibitory currents2
Increased
Description: Increased frequency of spontaneous mipscs in somatosensory cortex, compared to wild type
Exp Paradigm: Whole cell patch-clamp recordings
 Whole-cell patch clamp
 Unreported
Synaptic transmission: inhibitory5
Decreased
Description: Mutants show decrease in enteric gabaergic neurotransmission measured by failure to extend colonic migrating motor complexes along the length of the colon in the presence of gaba-a receptor antagonists in acute ex vivo colons. mutants show no change in the number of cmmcs in the presence of gaba-a receptor antagonist cgp 54626 indicating the involvement of gaba-a receptor recific mechanism.
Exp Paradigm: Colons challenged by exposure to the gabaa receptor antagonists bicuculline or gabazine
 Immunofluorescence staining
 8-12 weeks
Spontaneous post synaptic events3
Increased
Description: Increased frequency of spontaneous mini gaba postsynaptic current events but no change in amplitude, compared to wild type
Exp Paradigm: Whole-cell voltage-clamp recordings
 Whole-cell patch clamp
 P4-p9
Synaptic transmission: excitatory2
Increased
Description: Increased fepsp, compared to wild type
Exp Paradigm: Field potential recordings: slope of epsp by range of stimulus (input/ output relationship)
 Field potential recordings
 Unreported
Neuronal ion channel activity2
Increased
Description: Increased decay time constant or nmdar-mediated response, compared to wild type
Exp Paradigm: Whole cell patch-clamp recordings
 Whole-cell patch clamp
 Unreported
Spontaneous post synaptic events: inhibitory currents1
Increased
Description: Increased frequency of spontaneous inhibitory mini events but no change in amplitude
Exp Paradigm: Whole cell patch-clamp recordings in layer 2-3 of somtosensory cortex
 Whole-cell patch clamp
 Unreported
Synaptic transmission: inhibitory1
Increased
Description: Increased amplitude of evoked inhibitory response
Exp Paradigm: Whole cell patch-clamp recordings in layer 2-3 of somtosensory cortex
 Whole-cell patch clamp
 Unreported
Social interaction1
Decreased
Description: Reduced social approach and preference for social interaction
Exp Paradigm: Social interaction
 Reciprocal social interaction test
 2-4 months
Social interaction2
Decreased
Description: Decreased exploration of social target, compared to wild type
Exp Paradigm: Caged adult social interaction test
 Reciprocal social interaction test
 Unreported
Social memory2
Decreased
Description: Decreased preference for novel social target, compared to wild type
Exp Paradigm: Three-chamber social approach test: social novelty
 Three-chamber social approach test
 Unreported
Spatial learning1
Increased
Description: Enhanced spatial learning
Exp Paradigm: Morris water maze test
 Morris water maze test
 2-4 months
Targeted expression1
Decreased
Description: Decreased expression of nl3 protein
Exp Paradigm: Western blot
 Western blot
 3 months
Protein expression level evidence2
Increased
Description: Increase level of nr2b, nr2a subunits, compared to wild type
Exp Paradigm: Western blot
 Western blot
 Unreported
Targeted expression2
Decreased
Description: Decrease in level of nl3, compared to wild type, compared to wild type
Exp Paradigm: Western blot
 Western blot
 Unreported
Protein expression level evidence1
Decreased
Description: Decreased expression of nl1 protein
Exp Paradigm: Western blot
 Western blot
 3 months
Protein expression level evidence2
Increased
Description: Increased level of excitatory postsynaptic scaffolding proteins psd95, sap102, compared to wild type
Exp Paradigm: Western blot
 Western blot
 Unreported
Targeted expression5
Decreased
Description: Mutants express the mutant allele and not the wildtype allele as expressed in controls.
Exp Paradigm: Ileum
 Quantitative pcr (qrt-pcr)
 8 weeks
Protein expression level evidence1
Increased
Description: Increased expression of inhibitory synapse protein markers: vgat and gephyrin
Exp Paradigm: Western blot
 Western blot
 3 months
Digestive system development5
 No change
 Gross necroscopy
 8-12 weeks
Size/growth5
 No change
 Body weight measurement
 8-12 weeks
Tissue weight5
 No change
 Measurement of tissue weight
 8-12 weeks
Anxiety1
 No change
 Elevated plus maze test
 2-4 months
Anxiety1
 No change
 Open field test
 2-4 months
Exploratory activity1
 No change
 Novel object recognition test
 2-4 months
Gene expression1
 No change
 Quantitative pcr (qrt-pcr)
 3 months
Protein expression level evidence2
 No change
 Western blot
 Unreported
Protein expression level evidence2
 No change
 Western blot
 Unreported
Protein expression level evidence3
 No change
 Peak-scaled non-stationary fluctuation analysis
 Unreported
Protein expression level evidence1
 No change
 Western blot
 3 months
General locomotor activity1
 No change
 Light-dark exploration test
 2-4 months
Motor coordination and balance1
 No change
 Accelerating rotarod test
 2-4 months
Brain morphology1
 No change
 Immunohistochemistry
 3 months
Brain morphology1
 No change
 Electron microscopy
 8 weeks
Neuronal number: enteric neurons5
 No change
 Immunofluorescence staining
 8-12 weeks
Neuronal number: enteric neurons: gabaergic5
 No change
 Immunofluorescence staining
 8-12 weeks
Synapse density2
 No change
 Fluorescence microscopy
 Unreported
Synapse density: excitatory1
 No change
 Immunohistochemistry
 3 months
Synaptic morphology2
 No change
 Electron microscopy
 Unreported
Membrane potential3
 No change
 Whole-cell patch clamp
 P4-p9
Neuronal ion channel activity3
 No change
 Whole-cell patch clamp
 P11-p15
Neurotransporter activity3
 No change
 Whole-cell patch clamp
 P11-p16
Presynaptic function: paired-pulse facilitation2
 No change
 Field potential recordings
 Unreported
Spontaneous post synaptic events: excitatory currents2
 No change
 Whole-cell patch clamp
 Unreported
Spontaneous post synaptic events: excitatory currents1
 No change
 Whole-cell patch clamp
 Unreported
Spontaneous post synaptic events: excitatory currents3
 No change
 Whole-cell patch clamp
 P11-p15
Spontaneous post synaptic events: excitatory currents3
 No change
 Whole-cell patch clamp
 P4-p9
Spontaneous post synaptic events: inhibitory currents2
 No change
 Whole-cell patch clamp
 Unreported
Synaptic neuroreceptor ratio (nmdar/ampar) dependent transmission3
 No change
 Whole-cell patch clamp
 P4-p9
Synaptic neuroreceptor ratio (nmdar/ampar) dependent transmission2
 No change
 Whole-cell patch clamp
 Unreported
Synaptic plasticity1
 No change
 Whole-cell patch clamp
 Unreported
Synaptic transmission: excitatory1
 No change
 Whole-cell patch clamp
 Unreported
Tonic currents through extrasynaptic receptors3
 No change
 Whole-cell patch clamp
 P11-p15
Voltage sensitivity of n-methyl d-aspartate (nmda) receptors2
 No change
 Whole-cell patch clamp
 Unreported
Digestive system function: gastrointestinal motility: peristaltic reflexes5
 No change
 Measurement of colonic motility
 8-12 weeks
Vision1
 No change
 Morris water maze test
 2-4 months
Inanimate object preference2
 No change
 Novel object recognition test
 Unreported
Social approach2
 No change
 Three-chamber social approach test
 Unreported
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_NLGN3_2_KO

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Motor coordination and balance3
Increased
Description: Normal initial coordination with increased learning rate, compared to male littermate controls
Exp Paradigm: Accelerating rotarod, nine trials 4 to 40 rpm in 300 s
 Accelerating rotarod test
 6 weeks
Spontaneous post synaptic events: inhibitory currents2
Increased
Description: Increased frequency of spontaneous mipscs in hippocampus, compared to wild type
Exp Paradigm: Whole cell patch-clamp recordings
 Whole-cell patch clamp
 Unreported
Spontaneous post synaptic events: excitatory currents2
Decreased
Description: Decreased frequency of spontaneous mepscs in hippocampus, compared to wild type
Exp Paradigm: Whole cell patch-clamp recordings
 Whole-cell patch clamp
 Unreported
Targeted expression1
Decreased
Description: Loss of expression of nl3 protein
Exp Paradigm: Western blot
 Western blot
 3 months
Protein expression level evidence1
Decreased
Description: Decreased expression of nl1 protein
Exp Paradigm: Western blot
 Western blot
 3 months
General characteristics1
 No change
 General observations
 Unreported
Protein expression level evidence1
 No change
 Western blot
 3 months
Protein expression level evidence1
 No change
 Western blot
 3 months
Synapse density: excitatory1
 No change
 Immunohistochemistry
 3 months
Synapse density: inhibitory1
 No change
 Immunohistochemistry
 3 months
Presynaptic function: paired-pulse facilitation2
 No change
 Field potential recordings
 Unreported
Spontaneous post synaptic events: excitatory currents1
 No change
 Whole-cell patch clamp
 Unreported
Spontaneous post synaptic events: inhibitory currents1
 No change
 Whole-cell patch clamp
 Unreported
Synaptic neuroreceptor ratio (nmdar/ampar) dependent transmission2
 No change
 Whole-cell patch clamp
 Unreported
Synaptic neuroreceptor ratio (nmdar/ampar) dependent transmission2
 No change
 Whole-cell patch clamp
 Unreported
Synaptic plasticity1
 No change
 Whole-cell patch clamp
 Unreported
Synaptic plasticity: hippocampal ltp2
 No change
 Field potential recordings
 Unreported
Synaptic transmission: excitatory2
 No change
 Field potential recordings
 Unreported
Synaptic transmission: excitatory1
 No change
 Whole-cell patch clamp
 Unreported
Synaptic transmission: inhibitory1
 No change
 Whole-cell patch clamp
 Unreported
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_NLGN3_4_KO

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Hyperactivity1
Increased
Description: Increased total distance traveled, mean velocity, compared to wild type
Exp Paradigm: Open field test, mice were not nave
 Open field test
 12-15 weeks
Hyperactivity1
Increased
Description: Increased total distance traveled, mean velocity, compared to wild type
Exp Paradigm: Elevated plus maze test
 Elevated plus maze test
 12-15 weeks
Brain size1
Decreased
Description: Decreased volume of brain, excluding olfactory bulb, cerebellum and brainstem
Exp Paradigm: Magnetic resonance imaging
 Magnetic resonance imaging (mri)
 12-15 weeks
Olfaction1
Decreased
Description: Decreased response, measured by increased latency in food finding, compared to wild type
Exp Paradigm: Buried food test with no cues, mice were not nave
 Buried food test
 12-15 weeks
Social memory1
Decreased
Description: Decreased preference for novel social target, compared to wild type
Exp Paradigm: Three-chamber social approach test: social novelty, mice were not nave
 Three-chamber social approach test
 12-15 weeks
Ultrasonic vocalization1
Decreased
Description: Decreased response, measured by increased latency to initiate ultrasonic vocalizations in respose to female in estrous and decreased number of calls
Exp Paradigm: Call latency towards an unfamiliar female mouse in estrous, mice were not nave
 Monitoring ultrasonic vocalizations
 12-15 weeks
Exploratory activity1
Increased
Description: Increased number of holes explored in hole-board test
Exp Paradigm: Hole-board test, mice were not nave
 Hole-board test
 12-15 weeks
Cognitive flexibility1
Increased
Description: Increased cognitive flexibility measured by decreased latency to reach hidden platform in new location on first trial, but no change in learning rate of new location, and no change in time spent in new target quadrant in probe trial after learning, compared to wild type
Exp Paradigm: Morris water maze test: reversal learning, 8 trials, mice were not nave
 Morris water maze test
 12-15 weeks
Cued or contextual fear conditioning: memory of cue1
Decreased
Description: Decreased memory, measured by decreased freezing time in response to acoustic cue, compared to wild type
Exp Paradigm: Fear conditioning test: acoustic cue-dependent
 Fear conditioning test
 12-15 weeks
Cued or contextual fear conditioning: memory of context1
Decreased
Description: Decreased memory, measured by decreased freezing time in response to context, compared to wild type
Exp Paradigm: Fear conditioning test: contextual
 Fear conditioning test
 12-15 weeks
Size/growth1
 No change
 General observations
 12-15 weeks
Anxiety1
 No change
 Elevated plus maze test
 12-15 weeks
Anxiety1
 No change
 Open field test
 12-15 weeks
Spatial learning1
 No change
 Morris water maze test
 12-15 weeks
Spatial learning1
 No change
 Morris water maze test
 12-15 weeks
Spatial reference memory1
 No change
 Morris water maze test
 12-15 weeks
Motor coordination and balance1
 No change
 Accelerating rotarod test
 12-15 weeks
Sensorimotor gating1
 No change
 Prepulse inhibition
 12-15 weeks
Taste1
 No change
 Sucrose preference test
 12-15 weeks
Social approach1
 No change
 Three-chamber social approach test
 12-15 weeks
Social interaction1
 No change
 Reciprocal social interaction test
 12-15 weeks
 Not Reported: Circadian sleep/wake cycle, Immune response, Maternal behavior, Molecular profile, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure

M_NLGN3_3_KI_R451C

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Rapid eye movement sleep (rems)1
Abnormal
Description: Mutants show reduced alpha power during rem sleep compared to controls. mutants show no change in the proportion of time spent in rem sleep, compared to controls, in the light or dark period.
Exp Paradigm: Proportion of time that the mice spent in each vigilance state and their distribution during the light and dark periods were recorded. powers of delta (14 hz), theta (58 hz) and alpha (912 hz) frequency bands were examined in each sleep/wake state over time as these are indicators of cortical arousal and sleep quality.
 Electroencephalogram/electromyogram (eeg/emg)
 4.5 months
Non rapid eye movement sleep (nrems)1
Abnormal
Description: Mutants show reduced theta and alpha powers during nrem sleep, compared to controls. mutants show no change in the proportion of time spent in nrem sleep, compared to controls, in the light or dark period.
Exp Paradigm: Proportion of time that the mice spent in each vigilance state and their distribution during the light and dark periods were recorded. powers of delta (14 hz), theta (58 hz) and alpha (912 hz) frequency bands were examined in each sleep/wake state over time as these are indicators of cortical arousal and sleep quality.
 Electroencephalogram/electromyogram (eeg/emg)
 4.5 months
Circadian rhythm1
Abnormal
Description: Mutants show reduced eeg power between 2 and 8 hz, compared to controls. mutants show no change in the distribution or proportion of time spent in wakefulness compared to controls, in the light or dark period. mutants show increased eeg sigma and beta powers during wakefulness compared to controls.
Exp Paradigm: Proportion of time that the mice spent in each vigilance state and their distribution during the light and dark periods were recorded. powers of delta (14 hz), theta (58 hz) and alpha (912 hz) frequency bands were examined in each sleep/wake state over time as these are indicators of cortical arousal and sleep quality.
 Electroencephalogram/electromyogram (eeg/emg)
 4.5 months
Sleep pattern1
Abnormal
Description: Mutants show no change in the sleep-wake episodes or episode durations in the light or dark phase, compared to controls. mutants show reduced delta power, compared to controls, which is an indicator of sleep depth.
Exp Paradigm: Proportion of time that the mice spent in each vigilance state and their distribution during the light and dark periods were recorded. powers of delta (14 hz), theta (58 hz) and alpha (912 hz) frequency bands were examined in each sleep/wake state over time as these are indicators of cortical arousal and sleep quality.
 Electroencephalogram/electromyogram (eeg/emg)
 4.5 months
Motor coordination and balance2
Increased
Description: Increased latency to fall in male nl3 mice
Exp Paradigm: Accelerating rota rod test
 Accelerating rotarod test
 Adult
Grip strength2
Decreased
Description: Shorter latency to fall in the wire hang test for nl3 males compared to wild types
Exp Paradigm: Wire hang test
 Wire hang test
 Adult
General locomotor activity2
Decreased
Description: Decreased rate of rearing (vertical) activity in nl3 male mice compared to wild types
Exp Paradigm: Open field test
 Open field test
 Adult
Righting response2
Decreased
Description: Delayed righting response in males and females
Exp Paradigm: Righting response test
 Righting reflex test
 P2-p6
Gait2
Abnormal
Description: Increased forepaw width, but no change in hindpaw width or stride length in nl3 females compared to wild types
Exp Paradigm: Footprint pattern analysis
 Footprint analysis
 Adult
Microglial number4
Increased
Description: Increased microglial density in the dentate gyrus but not hippocampus ca1 region
 Immunofluorescence staining
 2-5 months
Microglial morphology4
Abnormal
Description: No change in microglial morphology in the dentate gyrus; microglia somata were elongated in the ca1; soma eccentricity was increased in the ca1 region
 Immunofluorescence staining
 2-5 months
Astrocyte morphology4
Decreased
Description: Decrease in astrocyte branch length, the number of branch points, and cell radius and area in the dentate gyrus; no change in astrocyte morphology in the ca1
 Immunofluorescence staining
 2-5 months
Synaptic transmission: excitatory3
Increased
Description: Increased fepsp, compared to wild type
Exp Paradigm: Field potential recordings: slope of epsp by range of stimulus (input/ output relationship)
 Field potential recordings
 Unreported
Startle response: acoustic stimulus2
Decreased
Description: Decreased startle response to 100-db, 110-db and 120-db acoustic stimuli
Exp Paradigm: Acoustic startle
 Prepulse inhibition
 Adult
Social scent marking or recognition2
Increased
Description: In females, shorter latency to reach nest area, nl3 females compared to wild types
Exp Paradigm: Homing test, females
 Homing test
 P9
Ultrasonic vocalization2
Decreased
Description: Decreased ultrasonic vocalization calls in male pups, but no change in duration, peak frequency or amplitude of calls, compared to wild types
Exp Paradigm: Maternal separation
 Monitoring ultrasonic vocalizations
 P8
Size/growth2
Decreased
Description: Decreased body weight in nl3 females, compared to wild types
Exp Paradigm: General observations
 General observations
 Adult
Size/growth2
Decreased
Description: Decreased body weight in female nl3 pups, compared to wild type
Exp Paradigm: General observations
 General observations
 P6-p12
Size/growth2
Increased
Description: Increased body weight in male nl3 pups, compared to wild type
Exp Paradigm: General observations
 General observations
 P6-p11
Targeted expression4
Decreased
Description: Neuroligin 3 protein expression was dramatically decreased in cortical, striatal and cerebellar tissue samples
 Western blot
 3 months
Protein expression: In situ protein expression4
Abnormal
Description: Increased striatal postsynaptic density 95 (psd-95) protein levels; decreased cortical expression of synaptosomal-associated protein 25 (snap-25); no change in gfap expression in cortex, striatum or cerebellum
 Western blot
 3 months
Ultrasonic vocalization2
 No change
 Monitoring ultrasonic vocalizations
 P2-p11
Size/growth2
 No change
 General observations
 Adult
Anxiety2
 No change
 Elevated plus maze test
 Adult
Cognitive flexibility2
 No change
 Morris water maze test
 Adult
Cued or contextual fear conditioning2
 No change
 Fear conditioning test
 Adult
Spatial learning2
 No change
 Morris water maze test
 Adult
Spatial reference memory2
 No change
 Morris water maze test
 Adult
Gait2
 No change
 Footprint analysis
 Adult
General locomotor activity2
 No change
 Open field test
 Adult
General locomotor activity: ambulatory activity2
 No change
 Open field test
 Adult
Motor coordination and balance2
 No change
 Accelerating rotarod test
 Adult
Astrocyte number4
 No change
 Immunofluorescence staining
 2-5 months
Hearing2
 No change
 Prepulse inhibition
 Adult
Sensorimotor gating2
 No change
 Prepulse inhibition
 Adult
Social approach2
 No change
 Three-chamber social approach test
 Adult
Social interaction2
 No change
 Reciprocal social interaction test
 P19-p23
Social scent marking or recognition2
 No change
 Homing test
 P9
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_NLGN3_16_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Motor coordination and balance1
Decreased
Description: Mutants show decreased motor coordination compared to controls measured by the increased step time. however, mutants show no change in the number of missteps or the decrease in the number of missteps over trials, compared to controls.
Exp Paradigm: Number of runs, missteps and step time was measured.
 Erasmus ladder test
 2-3 months
Synapse density3
Increased
Description: Increase in oxtr puncta in the vta th positive neurons
Exp Paradigm: oxtr
 Immunohistochemistry
 Adult
Neuroreceptor levels: glutamate receptors: nmda receptors1
Increased
Description: Mutants show increased in mglur1alpha protein but not transcript, compared to controls. mutants show no change in the expression of mglur2 and mglur7, compared to controls.
Exp Paradigm: Western blot
 Western blot
 2-3 months
Neuroreceptor levels: glutamate receptors: nmda receptors1
Increased
Description: Mutants show increased in mglur1alpha protein but not transcript, compared to controls. mutants show no change in the expression of mglur2 and mglur7, compared to controls.
Exp Paradigm: Quantitative pcr (qrt-pcr)
 Quantitative pcr (qrt-pcr)
 2-3 months
Anatomical projections and connectivity1
Abnormal
Description: Mutants show invasion of vglut2+ terminals into the distal molecular layer and increased density of vglut2 positive puncta on distal purkinje cell dendritic trees, compared to controls.
Exp Paradigm: NA
 Histology
 2-3 months
Synaptic plasticity: cerebellar ltd1
Decreased
Description: Mutants show no cerebellar ltd compared to wildtype controls that show persistent reduction of epsc amplitudes on application of the group i mglur agonist dhpg.
Exp Paradigm: Reduction of epsc amplitudes on application of the group i mglur agonist dhpg was measured in cerebellar slices.
 Whole-cell patch clamp
 2-3 months
Miniature post synaptic current amplitude: excitatory1
Increased
Description: Mutants show elevated evoked epsc amplitude in climbing fibers compared to controls.
Exp Paradigm: Evoked epsc amplitude was measured in climbing fibers.
 Whole-cell patch clamp
 2-3 months
Miniature post synaptic current amplitude: excitatory1
Decreased
Description: Mutants show decreased mepscs in purkinjee cells compared to controls.
Exp Paradigm: NA
 Whole-cell patch clamp
 3-4 weeks
Action potential property: firing rate3
Decreased
Description: Slightly reduced frequency of baseline firing of vta da neurons; bath application of oxytocin increased firing frequency in cells from wild-type mice but had no effect in mutant slices
 Whole-cell current clamp
 P27-35
Repetitive digging3
Decreased
Description: Decreased numbers of marbles buried
 Marble-burying test
 4 weeks
Social memory3
Decreased
Description: Decreased social recognition index
 Habituation-dishabituation test
 4 weeks
Social interaction3
Decreased
Description: Decreased time spent in social interaction
 Habituation-dishabituation test
 4 weeks
Social memory3
Decreased
Description: Impaired social novelty responses measured by decrease in time spent interacting with an unfamiliar mouse on the 5ht trial; no change in progressive decrease in time spent interacting with a social stimulus on successive trials
 Habituation-dishabituation test
 4 weeks
Targeted expression2
Decreased
Description: Mutants show decreased expression of nlgn3 compared to controls.
Exp Paradigm: Calbindin and actin are used as loading controls.
 Western blot
 Unreported
Protein phosphorylation1
Increased
Description: Mutants show increase in basal glua2 phosphorylation at serine 880 compared to the wild-type. however, upon dhpg stimulation, phospho-glua2 levels were decreased in mutant mice but increased in wildtype mice, probably due to mglur-stimulated degradation of the phosphorylated form of glua2
Exp Paradigm: Dhpg, a potent agonist of group i metabotropic glutamate receptors mglur1 and mglur5, is used in a functional assay.
 Western blot
 2-3 months
Regulation of translation3
Abnormal
Description: Signaling-dependent disruption of translation homeostasis in the ventral tegmental area indicated by increased incorporation of aha in vta da neurons
 Immunohistochemistry
 4 weeks
Protein localization: synapse1
Decreased
Description: Mutants show no nlgn3 protein localization in vglut2 positive or vgat positive synapses of purkinje cells and climbing fibers compared to controls.
Exp Paradigm: NA
 Histology
 2-3 months
Targeted expression1
Decreased
Description: Mutants show no nlgn3 protein expression in cerebellar glomerular layer cells and the mossy fiber terminals in the inner granular layer of the cerebellum, compared to controls.
Exp Paradigm: Western blot
 Western blot
 2-3 months
Regulation of translation3
Abnormal
Description: Dysregulation of translational machinery in vta tissue showing increase in core proteins of cytoplasmic but not mitochondrial ribosomes
 Tandem mass tagging (TMT)
 4 weeks
Gene expression3
Increased
Description: Increase in oxtr mrna in vta da neurons indicating impaired oxytocin signalling in dopaminergic neurons
Exp Paradigm: oxtr
 Fluorescence in situ hybridization (FISH)
 Adult
Targeted expression1
Decreased
Description: Mutants show no nlgn3 protein expression in cerebellar glomerular layer cells and the mossy fiber terminals in the inner granular layer of the cerebellum, compared to controls.
Exp Paradigm: Histology
 Histology
 2-3 months
Proteomic profile diversity3
Abnormal
Description: Dysregulation of protein transport, cell adhesion, mrna translation, membrane trafficking and g-protein-coupled receptor (gpcr) signaling
 Shotgun sequencing
 Adult
Size/growth3
 No change
 Marble-burying test
 4 weeks
Anxiety3
 No change
 Open field test
 4 weeks
Exploratory activity: Habituation3
 No change
 Habituation-dishabituation test
 4 weeks
Object recognition memory3
 No change
 Habituation-dishabituation test
 4 weeks
Gene expression1
 No change
 Quantitative pcr (qrt-pcr)
 2-3 months
Protein expression level evidence2
 No change
 Western blot
 Unreported
Protein expression level evidence1
 No change
 Histology
 2-3 months
Protein expression level evidence1
 No change
 Western blot
 2-3 months
Protein expression level evidence3
 No change
 Western blot
 4 weeks
General locomotor activity3
 No change
 Open field test
 4 weeks
Anatomical projections and connectivity3
 No change
 Immunohistochemistry
 Adult
Cerebellar morphology1
 No change
 Histology
 2-3 months
Neuronal number1
 No change
 Whole-cell patch clamp
 2-3 months
Neuronal number: Oxytocin expressing3
 No change
 Immunohistochemistry
 Adult
Neuroreceptor levels: glutamate receptors: nmda receptors1
 No change
 Western blot
 2-3 months
Neuroreceptor levels: OXT3
 No change
 Targeted parallel reaction monitoring assay (PRM LC-MS)
 Adult
Neuroreceptor levels: Vasopressin3
 No change
 Fluorescence in situ hybridization (FISH)
 Adult
Neuroreceptor levels: Vasopressin3
 No change
 Targeted parallel reaction monitoring assay (PRM LC-MS)
 Adult
Synapse density1
 No change
 Immunohistochemistry
 2-3 months
Decay kinetics of miniature post synaptic currents1
 No change
 Whole-cell patch clamp
 2-3 months
Hyperpolarization activated cation currents3
 No change
 Whole-cell patch clamp
 P27-35
Intrinsic membrane properties3
 No change
 Whole-cell current clamp
 P27-35
Membrane potential3
 No change
 Whole-cell current clamp
 P27-35
Presynaptic function: paired-pulse facilitation1
 No change
 Paired-pulse ratio
 2-3 months
Synaptic plasticity: cerebellar ltd2
 No change
 Whole-cell patch clamp
 P21-25
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_NLGN3_10_CKO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Motor coordination and balance1
Increased
Description: Normal initial coordination with increased learning rate, compared to nl3-cko littermate controls
Exp Paradigm: Accelerating rotarod, six trials 4 to 40 rpm in 300 s, six more trials 8 to 80 rpm in 300 s
 Accelerating rotarod test
 6 weeks
Hyperactivity1
Increased
Description: Increased total distance traveled and increased number of ambulatory episodes, compared to nl3-cko littermate controls
Exp Paradigm: Open field test, illuminated 60-minute session
 Open field test
 6 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_NLGN3_11_CKO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Hyperactivity1
 No change
 Open field test
 6 weeks
Motor coordination and balance1
 No change
 Accelerating rotarod test
 6 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_NLGN3_12_KI_R451C_D1-CRE

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Motor coordination and balance1
Increased
Description: Normal initial coordination with increased learning rate, compared to nl3-cko littermate controls
Exp Paradigm: Accelerating rotarod, six trials 4 to 40 rpm in 300 s, six more trials 8 to 80 rpm in 300 s
 Accelerating rotarod test
 6 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_NLGN3_13_CKO_HM_DS

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Hyperactivity1
 No change
 Open field test
 6 weeks
Motor coordination and balance1
 No change
 Accelerating rotarod test
 6 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_NLGN3_14_CKO_HM_NAC

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Motor coordination and balance1
Increased
Description: Normal initial coordination with increased learning rate, compared to nl3-cko littermate controls injected with catalytically inactive cre
Exp Paradigm: Accelerating rotarod, six trials 4 to 40 rpm in 300 s, six more trials 8 to 80 rpm in 300 s
 Accelerating rotarod test
 6 weeks
Hyperactivity1
Increased
Description: Increased total distance traveled and increased number of ambulatory episodes, compared to nl3-cko littermate controls injected with catalytically inactive cre
Exp Paradigm: Open field test, illuminated 60-minute session
 Open field test
 6 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_NLGN3_5_KO

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Motor coordination and balance1
Increased
Description: Normal initial coordination with increased learning rate, compared to male littermate controls
Exp Paradigm: Accelerating rotarod, six trials 4 to 40 rpm in 300 s, six more trials 8 to 80 rpm in 300 s
 Accelerating rotarod test
 6 weeks
Hyperactivity1
Increased
Description: Increased total distance traveled and increased number of ambulatory episodes, compared to male littermate controls, no change in speed
Exp Paradigm: Open field test, illuminated 60-minute session
 Open field test
 6 weeks
Perseveration1
Increased
Description: Increased repetitive behavior with training by observed reduction of variability of vertical location of each step, step length and time between steps, compared to male littermate controls
Exp Paradigm: Accelerating rotarod, first 30 s of trial 7 and trial 12 (8 to 80 rpm)
 Accelerating rotarod test
 6 weeks
Stereotypy1
Increased
Description: Increased time spent ambulatory and performing stereotypic movements, increased number of wall jumps and abnormal bias in the direction of rotation during locomotion
Exp Paradigm: Open field test, illuminated 60-minute session
 Open field test
 6 weeks
Stereotypy1
Increased
Description: Increased force variance during periods of low mobility
Exp Paradigm: Force plate actometer assay, 25-minute sessions at similar time of day
 Force plate actometer test
 6 weeks
Anxiety1
 No change
 Open field test
 6 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Immune response, Learning & memory, Maternal behavior, Molecular profile, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Seizure, Sensory, Social behavior

M_NLGN3_6_KI_R451C

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Motor coordination and balance1
Increased
Description: Normal initial coordination with increased learning rate, compared to male littermate controls
Exp Paradigm: Accelerating rotarod, six trials 4 to 40 rpm in 300 s, six more trials 8 to 80 rpm in 300 s
 Accelerating rotarod test
 6 weeks
Hyperactivity1
Increased
Description: Increased total distance traveled and increased number of ambulatory episodes, compared to male littermate controls, no change in speed
Exp Paradigm: Open field test, illuminated 60-minute session
 Open field test
 6 weeks
Perseveration1
Increased
Description: Increased repetitive behavior with training by observed reduction of variability of vertical location of each step, step length and time between steps, compared to male littermate controls
Exp Paradigm: Accelerating rotarod, first 30 s of trial 7 and trial 12 (8 to 80 rpm)
 Accelerating rotarod test
 6 weeks
Stereotypy1
Increased
Description: Increased time spent ambulatory and performing stereotypic movements
Exp Paradigm: Open field test, illuminated 60-minute session
 Open field test
 6 weeks
Anxiety1
 No change
 Open field test
 6 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Immune response, Learning & memory, Maternal behavior, Molecular profile, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Seizure, Sensory, Social behavior

M_NLGN3_7_CKO_NESTIN-CRE

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Hyperactivity1
Increased
Description: Increased total distance traveled and increased number of ambulatory episodes, compared to nl3-cko littermate controls
Exp Paradigm: Open field test, illuminated 60-minute session
 Open field test
 6 weeks
Targeted expression1
Decreased
Description: Complete loss of nl3 protein in whole brain, compared to nl3-cko littermate controls
Exp Paradigm: Western blot
 Western blot
 4 weeks
Gene expression1
Decreased
Description: Complete loss of nlgn3 mrna in whole brain, compared to nl3-cko littermate controls
Exp Paradigm: Quantitative pcr (qrt-pcr)
 Quantitative pcr (qrt-pcr)
 4 weeks
Gene expression1
 No change
 Quantitative pcr (qrt-pcr)
 4 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_NLGN3_8_CKO_HM_PURKINJEN

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Hyperactivity1
Increased
Description: Increased total distance traveled and increased number of ambulatory episodes, compared to nl3-cko littermate controls
Exp Paradigm: Open field test, illuminated 60-minute session
 Open field test
 6 weeks
Miniature post synaptic current amplitude: excitatory2
Decreased
Description: Mutants show decreased amplitude of climbing-fiber excitatory postsynaptic currents compared to controls.
Exp Paradigm: Climbing fibers were identified by their characteristic all-or-none response.
 Whole-cell current clamp
 1.2 months
Targeted expression2
Decreased
Description: Mutants show decreased expression of nlgn3 compared to controls.
Exp Paradigm: Calbindin and actin are used as loading controls.
 Western blot
 Unreported
Protein expression level evidence2
 No change
 Western blot
 Unreported
Motor coordination and balance1
 No change
 Accelerating rotarod test
 6 weeks
Decay kinetics of miniature post synaptic currents2
 No change
 Whole-cell current clamp
 P21-25
Intrinsic membrane properties2
 No change
 Whole-cell patch clamp
 P21-25
Miniature post synaptic current amplitude: inhibitory2
 No change
 Whole-cell patch clamp
 P21-25
Miniature post synaptic current frequency: inhibitory2
 No change
 Whole-cell patch clamp
 P21-25
Presynaptic function: paired-pulse facilitation2
 No change
 Whole-cell current clamp
 1.2 months
Spontaneous post synaptic event amplitude: inhibitory currents2
 No change
 Whole-cell patch clamp
 P21-25
Spontaneous post synaptic events: inhibitory currents2
 No change
 Whole-cell patch clamp
 P21-25
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_NLGN3_8_CKO_L7-CRE

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Hyperactivity1
Increased
Description: Increased total distance traveled and increased number of ambulatory episodes, compared to nl3-cko littermate controls
Exp Paradigm: Open field test, illuminated 60-minute session
 Open field test
 6 weeks
Motor coordination and balance1
 No change
 Accelerating rotarod test
 6 weeks
 Not Reported:

M_NLGN3_9_CKO_HM_PVALBN

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Hypoactivity1
Increased
Description: Decreased total distance traveled and no significant change in number of ambulatory episodes, compared to nl3-cko littermate controls
Exp Paradigm: Open field test, illuminated 60-minute session
 Open field test
 6 weeks
Motor coordination and balance1
 No change
 Accelerating rotarod test
 6 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_NLGN3_1_KI_R451C_GEPH-GFP

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Dendritic architecture: spine turnover1
Increased
Description: Nlgn3r451c mice show increased turnover of gephyrin-negative puncta associated spines in the ssc compared to wild type mice
Exp Paradigm: Turnover of gephyrin-gfp negative puncta-associated spines was measured
 Two-photon microscopy
 3 weeks
Neuronal activation following behavioral stimulation: c-fos levels1
Decreased
Description: Nlgn3r451c mice have reduced density of c-fos positive cells in the barrel cortex region corresponding to row c of whiskers, in layers 2/3 compared to wild type mice
Exp Paradigm: All whiskers except row c were removed and mice exposed to enriched environment for 1 h before sacrifice
 Immunohistochemistry
 3 weeks
Dendritic architecture: spine density1
 No change
 Two-photon microscopy
 3 weeks
Dendritic architecture: spine turnover1
 No change
 Histology
 3 weeks
Synapse density: excitatory1
 No change
 Two-photon microscopy
 3 weeks
Neuronal activation following behavioral stimulation: c-fos levels1
 No change
 Immunohistochemistry
 3 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_NLGN3_1_KI_R451C_PSD95-GFP

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Dendritic architecture: spine turnover1
Increased
Description: Nlgn3r451c mice show increased turnover of psd95-positive puncta associated spines in the afc compared to wild type mice
Exp Paradigm: Turnover of psd-95 -gfp positive puncta of spines was measured
 Two-photon microscopy
 3 weeks
Dendritic architecture: spine density1
 No change
 Two-photon microscopy
 3 weeks
Dendritic architecture: spine turnover1
 No change
 Two-photon microscopy
 3 weeks
Synapse density: excitatory1
 No change
 Two-photon microscopy
 3 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_NLGN3_19_KO_HE

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
General locomotor activity: ambulatory activity1
Increased
Description: Mutants travel greater distance than controls.
Exp Paradigm: NA
 Open field test
 3-4 weeks, 2-4 months
Repetitive digging1
Increased
Description: Mutants from mixed genotype housing buried a larger number of marbles than mutants or wildtype in single genotype housing but buried less marbles than wildtype in mixed genotype housing.
Exp Paradigm: NA
 Marble-burying test
 2-4 month
Social scent marking or recognition1
Increased
Description: Mutant males from mgh showed increased interest toward social odors than non-social odors compared to control male mice in mgh.
Exp Paradigm: NA
 Olfactory discrimination test
 2-4 month
Social interaction: with juveniles1
Decreased
Description: Juvenile mutant mice from mixed genotype housing spent less time interacting with an unfamiliar adult female in juvenile mice, compared to controls housed in single genotypes.
Exp Paradigm: NA
 Reciprocal social interaction test
 3-4 weeks
Social dominance1
Decreased
Description: Mutant males from mixed group housing are pushed out of the tube with greater frequency compared to wildtype males from mixed group housing. mutant males from mgh show an absence of correlation between social rank as determined by the tube test and the number of ultrasonic vocalization whereas mutant males from sgh show a linear correlation between social rank and usv. a structured social hierarchy did not develop in mutant mice from mgh.
Exp Paradigm: NA
 Tube test of social dominance
 2-4 month
Ultrasonic vocalization: interaction induced: opposite sex stimulus1
Decreased
Description: Mutant males mice from mixed group housing (mgh) show decreased ultrasonic vocalization during courtship than wildtype males from mixed group housing. mutant males from mgh and sgh spent similar times emitting usvs in the presence of a female in estrus.
Exp Paradigm: NA
 Monitoring ultrasonic vocalizations
 2-4 month
Targeted expression1
Decreased
Description: Mutants show decreased expression of nlgn3 protein in the cerebellum, cortex, striatum, hippocampus, brainstem and thalamus compared to controls.
Exp Paradigm: NA
 Western blot
 2-4 month
Adaptation to dark phase1
 No change
 Home cage behavior
 2-4 month
Anxiety1
 No change
 Elevated plus maze test
 3-4 weeks, 2-4 months
Anxiety1
 No change
 Open field test
 3-4 weeks, 2-4 months
Thigmotaxis1
 No change
 Open field test
 2-4 month
Gene expression1
 No change
 Quantitative pcr (qrt-pcr)
 2-4 month
Spontaneous movement1
 No change
 Spontaneous movement analysis
 2-4 month
Hormone levels1
 No change
 Elisa
 2-4 month
 Not Reported: Developmental profile, Immune response, Learning & memory, Maternal behavior, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Seizure, Sensory

M_NLGN3_20_KO_HE

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
General locomotor activity: ambulatory activity1
Increased
Description: Mutants travel greater distance than controls. mutants do not show an increase in the number of beam breaks over 30 h compared to controls.
Exp Paradigm: NA
 Open field test
 3-4 weeks, 2-4 months
Repetitive digging1
Decreased
Description: Mutants from single genotype housing buried fewer marbles than wildtype in single genotype housing but buried less marbles than wildtype or controls in mixed genotype housing.
Exp Paradigm: NA
 Marble-burying test
 2-4 month
Social scent marking or recognition1
Increased
Description: Mutant males from sgh showed increased interest toward social odors than non-social odors compared to control male mice in sgh.
Exp Paradigm: NA
 Olfactory discrimination test
 2-4 month
Ultrasonic vocalization: interaction induced: opposite sex stimulus1
Decreased
Description: Mutant males mice from single group housing (sgh) show decreased ultrasonic vocalization during courtship than wildtype males from sgh. mutant males from mgh and sgh spent similar times emitting usvs in the presence of a female in estrus.
Exp Paradigm: NA
 Monitoring ultrasonic vocalizations
 2-4 month
Thigmotaxis1
Decreased
Description: Mutants spend less time along the wall of the open field compared to controls.
Exp Paradigm: NA
 Open field test
 2-4 month
Anxiety1
Decreased
Description: Mutants spent increased durations in the center of the open field compared to controls and mutants housed in mixed genotype groups.
Exp Paradigm: NA
 Open field test
 2-4 month
Targeted expression1
Decreased
Description: Mutants show decreased expression of nlgn3 protein in the cerebellum, cortex, striatum, hippocampus, brainstem and thalamus compared to controls.
Exp Paradigm: NA
 Western blot
 2-4 month
Adaptation to dark phase1
 No change
 Home cage behavior
 2-4 month
Anxiety1
 No change
 Elevated plus maze test
 3-4 weeks
Anxiety1
 No change
 Open field test
 3-4 weeks
Gene expression1
 No change
 Quantitative pcr (qrt-pcr)
 2-4 month
Spontaneous movement1
 No change
 Spontaneous movement analysis
 2-4 month
Social dominance1
 No change
 Tube test of social dominance
 2-4 month
Social interaction: with juveniles1
 No change
 Reciprocal social interaction test
 3-4 weeks
 Not Reported: Developmental profile, Immune response, Learning & memory, Maternal behavior, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Seizure, Sensory

M_NLGN3_22_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Anxiety1
 No change
 Elevated plus maze test
 3-4 weeks
Anxiety1
 No change
 Open field test
 3-4 weeks
General locomotor activity: ambulatory activity1
 No change
 Open field test
 3-4 weeks
Social interaction1
 No change
 Open field test
 3-4 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Immune response, Learning & memory, Maternal behavior, Molecular profile, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory

M_NLGN3_23_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
General locomotor activity: ambulatory activity1
Increased
Description: Female mutants conventionally reared show increase in total distance travelled on the open field compared to controls.
Exp Paradigm: NA
 Open field test
 2-4 month
Social interaction1
Decreased
Description: Female mutants conventionally reared show decrease in social interaction with an unfamiliar female compared to controls.
Exp Paradigm: NA
 Reciprocal social interaction test
 2-4 month
Thigmotaxis1
Decreased
Description: Female mutants conventionally reared show decrease in distance travelled by the wall of the open field compared to controls.
Exp Paradigm: NA
 Open field test
 2-4 month
Anxiety1
 No change
 Elevated plus maze test
 2-4 month
Anxiety1
 No change
 Elevated plus maze test
 3-4 weeks
Anxiety1
 No change
 Open field test
 3-4 weeks
General locomotor activity: ambulatory activity1
 No change
 Open field test
 3-4 weeks
Social interaction1
 No change
 Open field test
 3-4 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Immune response, Learning & memory, Maternal behavior, Molecular profile, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory

M_NLGN3_24_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Social interaction1
Decreased
Description: Female heterozygous mutant mice raised with nlgn3 null littermates spent less time in contact with an unfamiliar female than heterozygous females raised with wildtype littermates.
Exp Paradigm: NA
 Reciprocal social interaction test
 2-4 month
Anxiety1
 No change
 Elevated plus maze test
 2-4 month
Anxiety1
 No change
 Open field test
 2-4 month
Thigmotaxis1
 No change
 Open field test
 2-4 month
General locomotor activity: ambulatory activity1
 No change
 Open field test
 2-4 month
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Immune response, Learning & memory, Maternal behavior, Molecular profile, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory

M_NLGN3_25_KO_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Anxiety1
 No change
 Elevated plus maze test
 2-4 month
Thigmotaxis1
 No change
 Open field test
 2-4 month
General locomotor activity: ambulatory activity1
 No change
 Open field test
 2-4 month
Social interaction1
 No change
 Reciprocal social interaction test
 2-4 month
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Immune response, Learning & memory, Maternal behavior, Molecular profile, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory

M_NLGN3_26_KI_R451C

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Synaptic plasticity: striatal ltd1
Decreased
Description: Mutants show no change of the amplitude of evoked epsp upon high frequency stimulation compared to controls where high frequency stimulation induces ltd of of evoked epsps.
Exp Paradigm: Corticostrial slices were used for recordings.
 Whole-cell patch clamp
 2 month
Action potential property: amplitude1
 No change
 Whole-cell patch clamp
 2 month
Action potential property: firing pattern1
 No change
 Whole-cell patch clamp
 2 month
Action potential property: half-width1
 No change
 Whole-cell patch clamp
 2 month
Intrinsic membrane properties1
 No change
 Whole-cell patch clamp
 2 month
Membrane potential1
 No change
 Whole-cell patch clamp
 2 month
Miniature post synaptic current amplitude: excitatory1
 No change
 Whole-cell patch clamp
 2 month
Miniature post synaptic current frequency: excitatory1
 No change
 Whole-cell patch clamp
 2 month
Presynaptic function: paired-pulse facilitation1
 No change
 Whole-cell patch clamp
 2 month
Spontaneous post synaptic event amplitude: excitatory currents1
 No change
 Whole-cell patch clamp
 2 month
Spontaneous post synaptic event frequency: excitatory currents1
 No change
 Whole-cell patch clamp
 2 month
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_NLGN3_21_KI_R451C

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Hyperactivity2
Increased
Description: Mutants were hyperactive compared to controls.
Exp Paradigm: NA
 Home cage behavior
 2-3 months
General locomotor activity: ambulatory activity1
Increased
Description: Mutants travel greater distances measured by total beam breaks during a 2-hr session in locomotor boxes compared to control.
Exp Paradigm: NA
 Novel cage test
 2.3 to 6.6 months
General locomotor activity: ambulatory activity2
Increased
Description: Mutants show increase in total distance travelled compared to controls.
Exp Paradigm: NA
 Open field test
 2-3 months
General locomotor activity: ambulatory activity1
Increased
Description: Mutants mice travel a greater total distance compared to controls.
Exp Paradigm: NA
 Partition test
 2.3 to 6.6 months
Anatomical projections and connectivity2
Abnormal
Description: Mutants show a larger proportion of neurons in the mpfc phase-locking in the quiet state compared to controls. mutants show a lower proportion of neurons in the mpfc phase-locking during social interaction compared to controls.
Exp Paradigm: NA
 In vivo local field potential (lfp) recordings
 2-3 months
Electroencephalogram (eeg) signature2
Decreased
Description: During social sniffing mutants showed lower gamma band activity (3090 hz) than the wt mice.
Exp Paradigm: NA
 Electroencephalogram (eeg)
 2-3 months
Neuronal activation2
Decreased
Description: Mutants show decreased neuronal activation in the three-chamber test after social novelty compared to controls, measured by the number of c-fos expressing neurons. mutants show no change in neuronal activation in the three-chamber test after the sociability phase compared to controls, measured by the number of c-fos expressing neurons.
Exp Paradigm: Expression of the immediate-early gene c-fos was assessed in different brain regions of mice after each stage of the three-chamber test.
 Immunohistochemistry
 2-3 months
Action potential property: firing rate2
Abnormal
Description: Mutant neurons show higher firing rates during sniffing while another proportion show inhibition, compared to controls, indicating a tendency for decentralization and disruption in functional encoding through dysregulated discharges during social interaction.
Exp Paradigm: Firing rate changes in the quiet and social states were assessed by calculating the discrimination index.
 In vivo local field potential (lfp) recordings
 2-3 months
Network excitability2
Abnormal
Description: Mutants showed reduced coupling between the low- gamma amplitude and the theta phase but displayed stronger and wider coupling between high gamma and theta rhythms, especially during social sniffing whereas local field potentials (lfps) from the wt mice showed modulation of both low-gamma and high-gamma amplitudes by the theta phase during social interaction with novel or familiar conspecific mice. mutants show weaker strength of modulation between low gamma and theta when exploring a new environment compared to controls. mutants show, decentralized gamma bursts within a single theta cycle during sniffing, indicating impairment of local coordinated network activity in the mpfc during social behaviors.
Exp Paradigm: NA
 In vivo local field potential (lfp) recordings
 2-3 months
Intrinsic bursting events or spikes2
Decreased
Description: Mutants show impaired intrinsic excitability of mpfc fast spiking interneurons in response to step-current injection compared to controls, suggesting that the reduced excitability of fs interneurons in the mpfc of the mutant mice is associated with the social novelty deficit.
Exp Paradigm: NA
 Whole-cell patch clamp
 2-3 months
Startle response: acoustic stimulus1
Decreased
Description: Mutant mice show less acoustic startle to high decibel tones, compared to controls.
Exp Paradigm: Response to tones of increasing volume was measured.
 Acoustic startle reflex test
 2.3 to 6.6 months
Social memory2
Decreased
Description: Mutants show decreased preference for the unfamiliar mouse compared to controls.
Exp Paradigm: NA
 Three-chamber social approach test
 2-3 months
Nest building behavior1
Increased
Description: Mutants built slightly wider nests of similar heights compared to controls.
Exp Paradigm: NA
 Nest building assay
 2.3 to 6.6 months
Spatial reference memory1
Decreased
Description: Mutants show decreased preference for the target quadrant compared to controls, during the probe trial when the platform is removed on the 12th day after 11 days training. mutants show decreased preference for the target quadrant, 5 days after reversal training, compared to controls.
Exp Paradigm: NA
 Morris water maze test
 2.3 to 6.6 months
Signaling3
Abnormal
Description: lack of Shank2 and gephyrin on the PTPĪ“A3Bā?? beads in mutant cortical neurons; NRXN1Ī²-induced accumulation of Shank2 and gephyrin was unaltered and significantly increased in Nlgn3R/C cortical neurons, respectively, suggesting that the Nlgn3 R/C mutation impairs the non-canonical pathway
 Immunostaining
 Adult
Protein binding3
Decreased
Description: reduced the NLGN3 pulldown efficiency by NRXN1Ī² and PTPĪ“A3Bā?? to 40% and 20% of wild-type, respectively
 Co-immunoprecipitation
 Adult
Anxiety1
 No change
 Open field test
 2.3 to 6.6 months
Anxiety1
 No change
 Elevated plus maze test
 2.3 to 6.6 months
Anxiety2
 No change
 Open field test
 2-3 months
Anxiety1
 No change
 Light-dark exploration test
 2.3 to 6.6 months
Exploratory activity: habituation1
 No change
 Olfactory discrimination test
 2.3 to 6.6 months
Thigmotaxis1
 No change
 Open field test
 2.3 to 6.6 months
Thigmotaxis1
 No change
 Morris water maze test
 2.3 to 6.6 months
Cognitive flexibility1
 No change
 Morris water maze test
 2.3 to 6.6 months
Cued or contextual fear conditioning: memory of context1
 No change
 Fear conditioning test
 2.3 to 6.6 months
Cued or contextual fear conditioning: memory of cue1
 No change
 Fear conditioning test
 2.3 to 6.6 months
Object recognition memory2
 No change
 Novel object recognition test
 2-3 months
Spatial working memory2
 No change
 Morris water maze test
 2-3 months
Spatial working memory1
 No change
 Morris water maze test
 2.3 to 6.6 months
Spatial working memory2
 No change
 Y-maze test
 2-3 months
General locomotor activity: ambulatory activity1
 No change
 Open field test
 2.3 to 6.6 months
Motor learning1
 No change
 Accelerating rotarod test
 2.3 to 6.6 months
Swimming ability1
 No change
 Morris water maze test
 2.3 to 6.6 months
Intrinsic bursting events or spikes2
 No change
 Whole-cell patch clamp
 2-3 months
Olfaction1
 No change
 Olfactory discrimination test
 2.3 to 6.6 months
Olfaction1
 No change
 Buried food test
 2.3 to 6.6 months
Sensorimotor gating1
 No change
 Prepulse inhibition
 2.3 to 6.6 months
Social approach2
 No change
 Three-chamber social approach test
 2-3 months
Social interaction1
 No change
 Partition test
 2.3 to 6.6 months
Social interaction: with juveniles1
 No change
 Three-chamber social approach test
 2.3 to 6.6 months
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Immune response, Maternal behavior, Molecular profile, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory

M_NLGN3_27_KD

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Targeted expression1
Decreased
Description: Mutants show decreased nl3 protein in the medial prefrontal cortex compared to controls.
Exp Paradigm: NA
 Western blot
 4.5 months
Targeted expression1
Decreased
Description: Mutants show decreased levels of nlgn3 mrna compared to controls.
Exp Paradigm: NA
 Quantitative pcr (qrt-pcr)
 2.75 months
Social approach1
 No change
 Three-chamber social approach test
 2-3 months
Social memory1
 No change
 Three-chamber social approach test
 2-3 months
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory

M_NLGN3_28_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
General locomotor activity1
Increased
Description: Global nlgn3 mutants show increased velocity of locomotion in the open field compared with controls.
Exp Paradigm: NA
 Open field test
 Adult
Neuroreceptor activity1
Abnormal
Description: Global nlgn3 knockout mice show increase in rectification index of ampar mediated currents compared with controls, indicating aberrant increase of glua2-lacking ampars in nlgn3 deficient vta da neurons.
Exp Paradigm: NA
 Whole-cell patch clamp
 4-8 weeks
Repetitive digging1
Decreased
Description: Global nlgn3 mutants show a decrease in the total number of marbles buried compared with controls.
Exp Paradigm: NA
 Marble-burying test
 Adult
Social habituation1
Decreased
Description: Global nlgn3 mutants show overall lower interaction times and no significant habituation compared with controls.
Exp Paradigm: NA
 Habituation-dishabituation test
 Adult
Social dishabituation1
Decreased
Description: Global nlgn3 mutants show no increase in interaction in response to the nonfamiliar conspecific mice as seen in controls.
Exp Paradigm: NA
 Habituation-dishabituation test
 Adult
Reward reinforced choice behavior1
Decreased
Description: Global nlgn3 mutants did not develop a preference for the social compartments when conditioned in a conditioned place preference paradigm with a familiar mouse, compared with wildtype controls.
Exp Paradigm: NA
 Conditioned place preference test
 Adult
Olfactory learning and memory1
Decreased
Description: Global nlgn3 mutants show decrease in response when presented a second novel social odor compared with controls.
Exp Paradigm: NA
 Olfactory discrimination test
 Adult
Exploratory activity: habituation1
 No change
 Habituation-dishabituation test
 Adult
Object recognition memory1
 No change
 Novel object recognition test
 Adult
Olfaction1
 No change
 Olfactory discrimination test
 Adult
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Immune response, Maternal behavior, Molecular profile, Neuroanatomy / ultrastructure / cytoarchitecture, Physiological parameters, Seizure

M_NLGN3_29_KD

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Synaptic plasticity: ventral tegmental area ltp1
Decreased
Description: Vta specific nlgn3 knockdown mutant mice show lack of synaptic plasticity induced by exposure to nonfamiliar conspecifics compared with controls. glua2-lacking ampars in vta, abnormally elevated in dopaminergic vta specific nlgn3 knockdown mutants show no further increase 24 hours after exposure to nonfamiliar social stimulus, indicating glua2 lacking ampars in vta da neurons is associated with impaired response to novel social stimulus.
Exp Paradigm: NA
 Whole-cell patch clamp
 4-8 weeks
Neuroreceptor activity1
Abnormal
Description: Vta specific nlgn3 knockdown mutant mice show increase in rectification index of ampar mediated currents compared with controls, indicating aberrant increase of glua2-lacking ampars in nlgn3 deficient vta da neurons.
Exp Paradigm: NA
 Whole-cell patch clamp
 4-8 weeks
Social habituation1
Decreased
Description: Mutants show overall lower interaction times and no significant habituation compared with controls.
Exp Paradigm: NA
 Habituation-dishabituation test
 2 months
Social dishabituation1
Decreased
Description: Mutants show no increase in interaction in response to the nonfamiliar conspecific mice as seen in controls.
Exp Paradigm: NA
 Habituation-dishabituation test
 2 months
Reward reinforced choice behavior1
Decreased
Description: Mutants did not develop a preference for the social compartments when conditioned in a conditioned place preference paradigm with a familiar mouse, compared with controls.
Exp Paradigm: NA
 Conditioned place preference test
 1.2-1.5 months
Targeted expression1
Decreased
Description: Mutants show gfp immunofluorescence in infected neurons in the vta compared with controls. tyrosine hydroxylase positive da neurons infected with aav2-dio-mirnlgn3 are detected in the vta, substantia nigra pars compacta (snc), dorsal raphe nucleus and retrorubral area (rr).
Exp Paradigm: NA
 Immunohistochemistry
 ~11 weeks
Targeted expression1
Decreased
Description: Mutants show decrease in nlgn3 protein expression in cortical neurons compared with controls.
Exp Paradigm: NA
 Western blot
 ~11 weeks
Object recognition memory1
 No change
 Novel object recognition test
 1.7 months
Olfactory learning and memory1
 No change
 Olfactory discrimination test
 Not specified
Protein expression level evidence1
 No change
 Western blot
 ~11 weeks
General locomotor activity1
 No change
 Open field test
 1.7 months
Repetitive digging1
 No change
 Marble-burying test
 2.7 months
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Maternal behavior, Neuroanatomy / ultrastructure / cytoarchitecture, Physiological parameters, Seizure, Sensory

M_NLGN3_30_KD

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Social habituation1
Decreased
Description: Mutants show overall lower interaction times, no significant habituation and showed no increase in interaction in response to the nonfamiliar conspecific mice as seen in controls.
Exp Paradigm: NA
 Habituation-dishabituation test
 Adult
Reward reinforced choice behavior1
Decreased
Description: Mutants did not develop a preference for the social compartments when conditioned in a conditioned place preference paradigm with a familiar mouse, compared with controls.
Exp Paradigm: NA
 Conditioned place preference test
 Adult
Targeted expression1
Decreased
Description: Mutants show gfp immunofluorescence in infected neurons in the vta compared with controls. tyrosine hydroxylase positive da neurons infected with aav2-dio-mirnlgn3 are detected in the vta and substantia nigra pars compacta (snc).
Exp Paradigm: NA
 Immunohistochemistry
 Adult
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Maternal behavior, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory

M_NLGN3_31_KI_HE_R451C

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Synapse density: inhibitory1
Increased
Description: Mutants show no change in gephyrin expression in the cerebellum compared with controls, a marker of inhibitory synapses.
Exp Paradigm: NA
 Western blot
 2 months
Miniature post synaptic current frequency: excitatory1
Increased
Description: Mutants show increase in frequency of miniature spontaneous excitatory postsynatptic currents in the cerebellum compared with controls in the cerebellar purkinje cells.
Exp Paradigm: NA
 Whole-cell patch clamp
 2 months
Targeted expression1
Decreased
Description: Mutants show decrease in nlgn3 expression and decrease in the progressive increase in expression in the whole brain and in the cerebellum, cortex and hippocampus, compared with controls.
Exp Paradigm: NA
 Western blot
 E12, 14, 16, 18, p5, 3 weeks, 2 months
Protein expression level evidence1
Increased
Description: Mutants show increased bip protein level in the cerebellum but not in the hippocampus or cortex compared with controls. mutants show increased level of nlgn1 protein compared with controls, usually located in excitatory synapses.
Exp Paradigm: NA
 Western blot
 2 months
Protein phosphorylation1
Increased
Description: Mutants show increase in phosphorylated eif2alpha levels in the cerebellum but not in the hippocampus or cortex compared with controls,
Exp Paradigm: NA
 Western blot
 2 months
Protein degradation: proteasome1
Increased
Description: Mutants show increased mutant protein levels in the brain following treatment with proteasomal inhibitor, compared with control, indicating preferential proteasomal degradation of the mutant protein.
Exp Paradigm: Mice were injected with proteasome inhibitor mg132 between p4 and p20.
 Western blot
 P20
Protein localization: endoplasmic reticulum1
Increased
Description: Mutants show that r451c mutant protein is partially retained in the endoplasmic reticulum compared to controls, as indicated by immature n-linked glycosylation detectable through endoglycosidase h sensitivity.
Exp Paradigm: Endoglycosidase h enzymatic assay
 Western blot
 E18
Gene expression1
Increased
Description: Mutants show brain region specific increase in activation of the upr pathway during development compared with controls, as measured by the levels of the chaperone bip in the cerebellum but not the encephalon. mutants show increase in bip levels in the cerebellum compared to controls but not in the hippocampus or cerebral cortex, during adulthood. mutants show increase in tunicamycin induced upr activation in the cerebellum but not in the hippocampus compared with controls.
Exp Paradigm: NA
 Quantitative pcr (qrt-pcr)
 E18, 2months
Protein expression: in situ protein expression1
Abnormal
Description: Mutants show increased and differently distributed expression of kdel containing er proteins, chaperones bip, grp94, and pdi, compared with controls, in cerebellar purkinje cells and misexpression of kdel proteins in the granule layer in the mutants.
Exp Paradigm: NA
 Western blot
 2 months
Protein expression level evidence1
 No change
 Western blot
 2 months
Synapse density: excitatory1
 No change
 Western blot
 2 months
Miniature post synaptic current amplitude: excitatory1
 No change
 Whole-cell patch clamp
 2 months
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Motor phenotype, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_NLGN3_18_KD

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Repetitive digging1
Decreased
Description: Nlgn3-sirna injected mice show decrease in repetitive digging compared with controls.
Exp Paradigm: NA
 Home cage behavior
 Adult
Self grooming: perseveration1
Increased
Description: Nlgn3-sirna injected mice show increase in repetitive self-grooming compared with controls.
Exp Paradigm: NA
 Grooming behavior assessments
 Adult
Object recognition memory1
Decreased
Description: Nlgn3-sirna injected mice show decrease in time spent with an unfamiliar object over a familiar object compared with controls.
Exp Paradigm: NA
 Object preference test
 Adult
Targeted expression1
Decreased
Description: Nlgn3-sirna injected mice show decrease in nlgn3 transcript in the dorsal striatum, 2 days after injection.
Exp Paradigm: Striatal tissue was used for qrt pcr.
 Quantitative pcr (qrt-pcr)
 Adult
Social memory1
 No change
 U-field assay
 Adult
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Maternal behavior, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Seizure, Sensory

M_NLGN3_32_KO_HE

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Hyperactivity1
Increased
Description: Increase in the number of beam breaks, but not screen touches and tray entries
 Home cage behavior
 12 weeks
Visual discrimination learning1
Increased
Description: No change in the number of trials from first presentation to 80% correct criterion; decrease in the number of correction trials to reach criterion
 Pairwise visual discrimination task
 12 weeks
Cognitive flexibility1
Increased
Description: Increase in percent of correct trials; decrease in perseveration index
 Pairwise visual discrimination task
 12 weeks
Reaction time: visual discrimination1
 No change
 Pairwise visual discrimination task
 12 weeks
Reward reinforced choice behavior1
 No change
 Operant conditioning paradigm
 12 weeks
 Not Reported:

M_NLGN3_32_KI_HE_HSE-AAA

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Synapse density1
Decreased
Description: impairment of the canonical and non-canonical synaptogenic pathways in these mutant mice by coculture assays using NRXN1Ī² and PTPĪ“A3Bā?? beads
 Immunostaining
 Adult
Social interaction1
Increased
Description: mutant mice spent more time in proximity with the other mice than their wild-type littermates; no change in number of counts of defensive upright posture measured by elevated head-head contacts throughout the test period
 Reciprocal social interaction test
 Adult
Social approach1
Increased
Description: mutants and their wild-type littermates spent more time in the chamber with the stranger mouse than in the chamber with the non-social empty cage, suggesting that disruption of the canonical NLGN3ā??NRXN interaction enhances sociability development
 Three-chamber social approach test
 Adult
Protein binding1
Abnormal
Description: in cortical neurons from Nlgn3hse mutant male mice, NRXN1Ī²-beads failed to induce accumulation of NLGN3 while Shank2 and gephyrin signals on the NRXN1Ī²-beads were attenuated but not completely abolished ; PTPĪ“A3Bā??-mediated accumulation of NLGN3 and gephyrin, but not Shank2, was upregulated
 Immunostaining
 Adult
Protein binding1
Increased
Description: anti-NLGN3 antibody coimmunoprecipitated more PTPĪ“ in the brains of the Nlgn3hse mutants than in those of wild-type littermates, indicating the canonical NLGN3ā??NRXN transsynaptic pathway is impaired
 Co-immunoprecipitation
 Adult
Protein degradation: proteasome1
 No change
 Immunostaining
 Adult
Protein expression: In situ protein expression1
 No change
 Western blot
 Adult
Motor coordination and balance1
 No change
 Accelerating rotarod test
 Adult
Synaptic transmission: inhibitory1
 No change
 Whole-cell patch clamp
 Adult
 Not Reported: Molecular profile

M_NLGN3_33_KI_HE_MF-AA

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Motor coordination and balance1
Increased
Description: increase in latency to fall off
 Accelerating rotarod test
 Adult
Synapse density1
Decreased
Description: impairment of the canonical and non-canonical synaptogenic pathways in these mutant mice by coculture assays using NRXN1Ī² and PTPĪ“A3Bā?? beads
 Immunostaining
 Adult
Miniature post synaptic current frequency: inhibitory1
Increased
Description: frequencies of both miniature inhibitory postsynaptic currents (mIPSC) were increased
 Whole-cell patch clamp
 Adult
Miniature post synaptic current frequency: excitatory1
Increased
Description: frequencies of both miniature excitatory postsynaptic currents (mEPSC) were increased
 Whole-cell patch clamp
 Adult
Social interaction1
Increased
Description: mutant mice spent more time in proximity with the other mice than their wild-type littermates; increase in number of head to head contacts; shorter duration in each stranger-cage-sniffing behavior than their wild-type littermates
 Reciprocal social interaction test
 Adult
Protein expression: In situ protein expression1
Decreased
Description: the expression of inhibitory synaptic proteins vesicular GABA transporter (VGAT) and gephyrin, was selectively upregulated, while those of the excitatory synaptic proteins vesicular glutamate transporter 1 (VGluT1) and PSD95 remained unaltered; immunostaining signal ratios for VGAT compared to VGluT1 in the cerebral cortex were higher
 Whole-cell patch clamp
 Adult
Protein binding1
Abnormal
Description: in cortical neurons from Nlgn3mf male mice, PTPĪ“A3Bā?? beads failed to induce NLGN3, Shank2, and gephyrin accumulation, while NRXN1Ī²-induced NLGN3 and gephyrin accumulation was markedly enhanced
 Immunostaining
 Adult
Protein binding1
Decreased
Description: anti-NLGN3 antibody failed to coimmunoprecipitate PTPĪ“ in the Nlgn3mf mice brain, indicating the non-canonical NLGN3ā??PTPĪ“ transsynaptic pathway is impaired
 Co-immunoprecipitation
 Adult
Protein degradation: proteasome1
 No change
 Immunostaining
 Adult
Social approach1
 No change
 Three-chamber social approach test
 Adult
 Not Reported: Molecular profile

M_NLGN3_34_CKO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Signaling1
Abnormal
Description: no accumulation of Shank2 or gephyrin was detected on the beads coated with PTPĪ“-meB(ā??), indicating that PTPĪ“-meB(ā??)s require NLGN3 to induce postsynaptic differentiation
 Immunostaining
 Adult
Synapse density1
 No change
 Immunostaining
 Adult
 Not Reported:


Interactor Symbol Interactor Name Interactor Organism Entrez ID Uniprot ID Interaction Type Evidence Reference
AES amino-terminal enhancer of split 166 Q08117 Y2H
Sakai Y , et al. 2011
AKT1 v-akt murine thymoma viral oncogene homolog 1 207 P31749 Y2H
Sakai Y , et al. 2011
ALPP CBS 250 P05187 Y2H
Shen C , et al. 2014
AP2A2 adaptor-related protein complex 2, alpha 2 subunit 161 O94973 Y2H
Shen C , et al. 2014
APC2 adenomatosis polyposis coli 2 10297 O95996 Y2H
Sakai Y , et al. 2011
ATF4 activating transcription factor 4 (tax-responsive enhancer element B67) 468 P18848 Y2H
Shen C , et al. 2014
ATXN1 ataxin 1 6310 P54253 Y2H
Sakai Y , et al. 2011
C1orf122 chromosome 1 open reading frame 122 127687 E9PQ13 Y2H
Shen C , et al. 2014
C1QA Complement C1q subcomponent subunit A 712 P02745 Y2H
Shen C , et al. 2014
CCAR2 Cell cycle and apoptosis regulator protein 2 57805 Q8N163 Y2H
Shen C , et al. 2014
CGB chorionic gonadotropin, beta polypeptide 1082 P01233 Y2H
Shen C , et al. 2014
COBL cordon-bleu homolog (mouse) 23242 O75128 Y2H
Sakai Y , et al. 2011
CTSD cathepsin D 1509 P07339 Y2H
Shen C , et al. 2014
CYP11A1 cytochrome P450, family 11, subfamily A, polypeptide 1 1583 P05108 Y2H; IP/WB; Immunofluorescence
Shen C , et al. 2014
DPEP2 Dipeptidase 2 64174 Q9H4A9 Y2H
Shen C , et al. 2014
EBPL Emopamil-binding protein-like 84650 Q9BY08 Y2H
Shen C , et al. 2014
EEF1A1 eukaryotic translation elongation factor 1 alpha 1 1915 P68104 Y2H; IP/WB; Immunofluorescence
Shen C , et al. 2014
EFEMP1 EGF containing fibulin-like extracellular matrix protein 1 2202 Q12805 Y2H
Sakai Y , et al. 2011
EFS embryonal Fyn-associated substrate 10278 O43281 Y2H
Shen C , et al. 2014
FAM115C TRPM8 channel-associated factor 2 285966 A6NFQ2 IP; LC-MS/MS
Huttlin EL , et al. 2015
FANCG Fanconi anemia, complementation group G 2189 O15287 Y2H
Shen C , et al. 2014
FBLN1 fibulin 1 2192 P23142 Y2H
Shen C , et al. 2014
FHOD1 formin homology 2 domain containing 1 29109 Q9Y613 Y2H
Shen C , et al. 2014
FKBP1A FK506 binding protein 1A, 12kDa 2280 P62942 Y2H
Shen C , et al. 2014
FLNA filamin A, alpha 2316 P21333 Y2H; IP/WB; Immunofluorescence
Shen C , et al. 2014
GDF15 Growth/differentiation factor 15 9518 Q99988 Y2H
Shen C , et al. 2014
GPR175 Transmembrane protein adipocyte-associated 1 131601 Q86W33 Y2H; IP/WB; Immunofluorescence
Shen C , et al. 2014
GUK1 guanylate kinase 1 2987 Q16774 Y2H
Shen C , et al. 2014
HID1 Protein HID1 283987 Q8IV36 Y2H
Shen C , et al. 2014
HIVEP1 human immunodeficiency virus type I enhancer binding protein 1 3096 P15822 Y2H
Sakai Y , et al. 2011
ITPRIP inositol 1,4,5-trisphosphate receptor interacting protein 85450 Q8IWB1 Y2H; IP/WB; Immunofluorescence
Shen C , et al. 2014
KIAA0922 KIAA0922 23240 A2VDJ0 IP; LC-MS/MS
Huttlin EL , et al. 2015
LGALS1 Galectin-1 3956 P09382 Y2H
Shen C , et al. 2014
MAN2C1 Alpha-mannosidase 2C1 4123 Q9NTJ4 Y2H
Shen C , et al. 2014
MAP1S microtubule-associated protein 1S 55201 Q66K74 Y2H
Shen C , et al. 2014
MEOX2 Homeobox protein MOX-2 4223 P50222 Y2H
Corominas R , et al. 2014
MIEN1 Migration and invasion enhancer 1 84299 Q9BRT3 Y2H
Shen C , et al. 2014
MT-CO2 Cytochrome c oxidase subunit 2 4513 P00403 Y2H; IP/WB; Immunofluorescence
Shen C , et al. 2014
NFATC4 nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 4 4776 Q14934 Y2H
Shen C , et al. 2014
NLGN1 neuroligin 1 22871 Q8N2Q7 IP; LC-MS/MS
Huttlin EL , et al. 2015
NLGN2 neuroligin 2 57555 Q8NFZ4 IP; LC-MS/MS
Huttlin EL , et al. 2015
NLGN4X neuroligin 4, X-linked 57502 Q8N0W4 IP; LC-MS/MS
Huttlin EL , et al. 2015
NLGN4Y Neuroligin-4, Y-linked 22829 Q8NFZ3 IP; LC-MS/MS
Huttlin EL , et al. 2015
NLRX1 NLR family member X1 79671 Q86UT6 IP; LC-MS/MS
Huttlin EL , et al. 2015
NRD1 nardilysin (N-arginine dibasic convertase) 4898 O43847 Y2H
Shen C , et al. 2014
OAZ1 ornithine decarboxylase antizyme 1 4946 P54368 Y2H
Shen C , et al. 2014
OR1F12 olfactory receptor, family 1, subfamily F, member 12 442179 Q8NHA8 Y2H
Shen C , et al. 2014
PICK1 protein interacting with PRKCA 1 9463 Q9NRD5 Y2H
Sakai Y , et al. 2011
PIK3CA phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha 5290 P42336 IP; LC-MS/MS
Huttlin EL , et al. 2015
PIK3CB phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta 5291 B4DER4 IP; LC-MS/MS
Huttlin EL , et al. 2015
PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (alpha) 5295 P27986 IP; LC-MS/MS
Huttlin EL , et al. 2015
PIK3R3 phosphoinositide-3-kinase, regulatory subunit 3 (gamma) 8503 Q8N381 IP; LC-MS/MS
Huttlin EL , et al. 2015
PKIB cAMP-dependent protein kinase inhibitor beta 5570 Q9C010 Y2H
Shen C , et al. 2014
PLB1 Phospholipase B1, membrane-associated 151056 Q6P1J6 Y2H
Shen C , et al. 2014
PLC4 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 5332 Q15147 Y2H
Shen C , et al. 2014
PSAP prosaposin 5660 P07602 Y2H
Shen C , et al. 2014
PSG1 Pregnancy-specific beta-1-glycoprotein 1 5669 P11464 Y2H
Shen C , et al. 2014
PSG11 pregnancy specific beta-1-glycoprotein 11 5680 Q9UQ72 Y2H
Shen C , et al. 2014
PSG3 Pregnancy-specific beta-1-glycoprotein 3 5671 Q16557 Y2H
Shen C , et al. 2014
PSG4 pregnancy specific beta-1-glycoprotein 4 5672 Q00888 Y2H
Shen C , et al. 2014
PSG5 Pregnancy-specific beta-1-glycoprotein 5 5673 Q15238 Y2H
Shen C , et al. 2014
PTPRD protein tyrosine phosphatase, receptor type, D 5789 P23468 IP; LC-MS/MS
Huttlin EL , et al. 2015
QARS glutaminyl-tRNA synthetase 5859 P47897 Y2H
Shen C , et al. 2014
QPRT Nicotinate-nucleotide pyrophosphorylase [carboxylating] 23475 Q15274 Y2H; IP/WB; Immunofluorescence
Shen C , et al. 2014
RBFOX1 RNA binding protein, fox-1 homolog (C. elegans) 1 54715 Q9NWB1 in silico target prediction; Splicing microarray
Zhang C , et al. 2008
RBM9 RNA binding protein fox-1 homolog 2 9606 O43251 Y2H
Sakai Y , et al. 2011
RECQL4 ATP-dependent DNA helicase Q4 9401 O94761 IP; LC-MS/MS
Huttlin EL , et al. 2015
SNTG2 syntrophin, gamma 2 54221 Q9NY99 IP
Yamakawa H , et al. 2007
SPAG5 sperm associated antigen 5 10615 Q96R06 Y2H
Shen C , et al. 2014
SPINT1 Kunitz-type protease inhibitor 1 6692 O43278 Y2H
Shen C , et al. 2014
SSR4 signal sequence receptor, delta 6748 P51571 Y2H
Shen C , et al. 2014
TDRD7 tudor domain containing 7 23424 Q8NHU6 Y2H
Sakai Y , et al. 2011
TMEM39A transmembrane protein 39A NM_018266 Q9NV64 IP; LC-MS/MS
Huttlin EL , et al. 2015
TNNT3 Troponin T, fast skeletal muscle 7140 P45378 Y2H
Shen C , et al. 2014
TRIM33 tripartite motif containing 33 51592 B3KN30 Y2H
Shen C , et al. 2014
TXNIP thioredoxin interacting protein 10628 Q9H3M7 Y2H
Shen C , et al. 2014
TYK2 tyrosine kinase 2 7297 P29597 IP; LC-MS/MS
Huttlin EL , et al. 2015
UBXN6 UBX domain protein 6 80700 Q9BZV1 Y2H
Shen C , et al. 2014
UQCRC1 Cytochrome b-c1 complex subunit 1, mitochondrial 7384 P31930 Y2H
Shen C , et al. 2014
UTP15 UTP15, U3 small nucleolar ribonucleoprotein, homolog (S. cerevisiae) 84135 Q8TED0 IP; LC-MS/MS
Huttlin EL , et al. 2015
FMR1 fragile X mental retardation 1 14265 P35922 HITS-CLIP
Darnell JC , et al. 2011
Nlgn1 neuroligin 1 192167 Q99K10 IP/WB
Budreck EC and Scheiffele P 2007
Nlgn2 neuroligin 2 216856 Q69ZK9 IP/WB
Budreck EC and Scheiffele P 2007
NRXN1 neurexin 1 18189 Q9CS84 IP/WB; IP; LC-MS/MS
Traunmller L , et al. 2016
SPARCL1 SPARC-like 1 13602 P70663 IP/WB; Cell surface binding assay
Singh SK , et al. 2016
Dlg2 discs, large homolog 2 (Drosophila) 64053 Q63622 Y2H
Irie M , et al. 1997
Dlg3 discs, large homolog 3 (Drosophila) 58948 Q62936 Y2H
Irie M , et al. 1997
Dlg4 discs, large homolog 4 (Drosophila) 29495 P31016 Y2H; Affinity chromatography
Irie M , et al. 1997
NRXN1 neurexin 1 60391 Q63373 IP; LC-MS/MS
Savas JN , et al. 2015
Nrxn1 neurexin 1 60391 Q63373 IP/WB
Ichtchenko K , et al. 1996
Nrxn2 neurexin 2 116595 Q63376 IP/WB
Ichtchenko K , et al. 1996
Nrxn3 neurexin 3 116508 Q07310 IP/WB
Ichtchenko K , et al. 1996
Rapgef4 Rap guanine nucleotide exchange factor (GEF) 4 252857 Q9Z1C7 IP/WB
Woolfrey KM , et al. 2009
Sorcs1 sortilin-related VPS10 domain containing receptor 1 309533 F1LUZ4 IP; LC-MS/MS; IP/WB; in vitro binding assay
Savas JN , et al. 2015

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