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.
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
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
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
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
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
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
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:
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:
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:
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:
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:
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:
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:
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:
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
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:
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:
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:
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:
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:
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:
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:
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:
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:
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:
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 )
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
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
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
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
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
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)
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)
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
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 PTPδ 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
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 PTPδ 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
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
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
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
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
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
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
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
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
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
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
Description: Increased sensitivity to ifenprodil, nr1/nr2b heterotetrameric-selective antagonist, compared to wild type
Exp Paradigm: Field potential recordings
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
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
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
Description: Increased fepsp, compared to wild type
Exp Paradigm: Field potential recordings: slope of epsp by range of stimulus (input/ output relationship)
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
Description: Abnormal structure of the fecal microbial community; cage environment and age contributed to microbial profiles; no change in microbial richness; no change in overall abundance of different bacterial phyla at 5 and 9 weeks; firmicutes and bacteroidetes (93%); proteobacteria (3%) and actinobacteria, candidate, cyanobacteria, and tenericutes (4%); no change in microbial diversity at 9 weeks but difference in the abundance of 6 otus
Exp Paradigm: NA
16s rrna gene sequence analysis for identification of bacteria
Digestive system function: gastrointestinal motility5
Increased
Description: Mutants show faster small intestine transit compared with controls. mutants show a higher ratio of dye front to the length of the small intestine compared with controls.
Exp Paradigm: Orally gavaged carmine red dye front was measured.
Description: Mutant fecal microbiota show difference in the carbon utilization of the fecal microbial communities. mutants show no change in microbial functional richness in fecal samples, measured as the number of different carbon sources the community could utilize. mutant fecal microbiota show higher utilization of glucosaminic acid compared with controls at 9weeks. mutant fecal microbiota show no change in the utilization of amide/amine at 9weeks. mutant fecal microbiota show marginal decrease in the utilization of carbohydrate i-erythritol at 9 weeks. mutant fecal microbiota show no change in the utilization of amino acid t-phenylalanine compare with controls at 9 weeks. mutants show no change in overall metabolic profiles.
Exp Paradigm: Carbon substrate utiliztion assay
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
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
Description: Decreased preference for novel social target, compared to wild type
Exp Paradigm: Three-chamber social approach test: social novelty, mice were not nave
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
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
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
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
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.
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.
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.
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.
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
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
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
Description: Increased fepsp, compared to wild type
Exp Paradigm: Field potential recordings: slope of epsp by range of stimulus (input/ output relationship)
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
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
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.
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
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
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)
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.
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.
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
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
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.
Description: Signaling-dependent disruption of translation homeostasis in the ventral tegmental area indicated by increased incorporation of aha in vta da neurons
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
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
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
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
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
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
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
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
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
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
Description: Increased force variance during periods of low mobility
Exp Paradigm: Force plate actometer assay, 25-minute sessions at similar time of day
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)
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
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
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
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)
Digestive system function: gastrointestinal motility: peristaltic reflexes2
Increased
Description: Nlgn3 knockin mutant mice show increased velocity of forward/peristaltic contractions, decreased duration and decreased start position; no change in velocity of reverse/anti-peristaltic contraction, and decreased duration.
Digestive system function: gastrointestinal motility: intestinal motility2
Abnormal
Description: Nlgn3 mutant mice show increased number of cecal motor complexes per 15 minutes, increased velocity, decreased duration, and no change in quiescence.
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
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
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.
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
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
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
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
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
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
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
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
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
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
Description: Mutants show decreased expression of nlgn3 protein in the cerebellum, cortex, striatum, hippocampus, brainstem and thalamus compared to controls.
Exp Paradigm: NA
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
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
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
Description: Mutant males in sgh show increased testosterone levels compared to control males in sgh.
Exp Paradigm: Testosterone levels were measured in urine.
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
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
Description: Mutants show decreased expression of nlgn3 protein in the cerebellum, cortex, striatum, hippocampus, brainstem and thalamus compared to controls.
Exp Paradigm: NA
Description: Female mutants conventionally reared show decrease in distance travelled by the wall of the open field compared to controls.
Exp Paradigm: NA
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
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.
Description: Mutants travel greater distances measured by total beam breaks during a 2-hr session in locomotor boxes compared to control.
Exp Paradigm: NA
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
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
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.
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.
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
Description: Mutant mice show less acoustic startle to high decibel tones, compared to controls.
Exp Paradigm: Response to tones of increasing volume was measured.
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
Description: lack of Shank2 and gephyrin on the PTPδA3Bâ?? beads in mutant cortical neurons; NRXN1β-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
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
Description: Global nlgn3 mutants show no increase in interaction in response to the nonfamiliar conspecific mice as seen in controls.
Exp Paradigm: NA
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
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
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
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
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
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
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
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
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
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
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
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
Description: Mutants show increase in phosphorylated eif2alpha levels in the cerebellum but not in the hippocampus or cortex compared with controls,
Exp Paradigm: NA
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.
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
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
Description: Nlgn3-sirna injected mice show decrease in time spent with an unfamiliar object over a familiar object compared with controls.
Exp Paradigm: NA
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.
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
Description: impairment of the canonical and non-canonical synaptogenic pathways in these mutant mice by coculture assays using NRXN1β and PTPδA3Bâ?? beads
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 NLGN3â??NRXN interaction enhances sociability development
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
Description: in cortical neurons from Nlgn3hse mutant male mice, NRXN1β-beads failed to induce accumulation of NLGN3 while Shank2 and gephyrin signals on the NRXN1β-beads were attenuated but not completely abolished ; PTPδA3Bâ??-mediated accumulation of NLGN3 and gephyrin, but not Shank2, was upregulated
Description: anti-NLGN3 antibody coimmunoprecipitated more PTPδ in the brains of the Nlgn3hse mutants than in those of wild-type littermates, indicating the canonical NLGN3â??NRXN transsynaptic pathway is impaired
Description: impairment of the canonical and non-canonical synaptogenic pathways in these mutant mice by coculture assays using NRXN1β and PTPδA3Bâ?? beads
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
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
Description: in cortical neurons from Nlgn3mf male mice, PTPδA3Bâ?? beads failed to induce NLGN3, Shank2, and gephyrin accumulation, while NRXN1β-induced NLGN3 and gephyrin accumulation was markedly enhanced
Description: anti-NLGN3 antibody failed to coimmunoprecipitate PTPδ in the Nlgn3mf mice brain, indicating the non-canonical NLGN3â??PTPδ transsynaptic pathway is impaired
Description: no accumulation of Shank2 or gephyrin was detected on the beads coated with PTPδ-meB(â??), indicating that PTPδ-meB(â??)s require NLGN3 to induce postsynaptic differentiation
