HELP     Sign In
Search

Relevance to Autism

In a genome-wide study, association was found between CNVs in the NLGN1 gene and autism in AGRE and ACC cohorts (European ancestry) (Glessner et al., 2009). In addition, a duplication of the NLGN1 gene was found in a patient with autism and mild intellectual disability (Leblond et al., 2012), and a rare mutation in NLGN1 has been identified in an individual with ASD (ORoak et al., 2012).

Molecular Function

This gene encodes a member of a family of neuronal cell surface proteins. 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
Autism genome-wide copy number variation reveals ubiquitin and neuronal genes.
ASD
Positive Association
Genome-wide gene-based analysis suggests an association between Neuroligin 1 (NLGN1) and post-traumatic stress disorder.
Post-traumatic stress disorder
Support
Whole-genome sequencing of quartet families with autism spectrum disorder.
ASD
Support
Prospective diagnostic analysis of copy number variants using SNP microarrays in individuals with autism spectrum disorders.
ASD
ID
Support
Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder.
ASD
Support
Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.
ASD
Support
Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders.
ASD
ID
Support
Variable phenotype expression in a family segregating microdeletions of the NRXN1 and MBD5 autism spectrum disorder susceptibility genes.
ASD, ADHD, ID
Macrocephaly
Highly Cited
Binding of neuroligins to PSD-95.
Highly Cited
Structures, alternative splicing, and neurexin binding of multiple neuroligins.
Highly Cited
Neuroligin 1: a splice site-specific ligand for beta-neurexins.
Recent Recommendation
LMO4 controls the balance between excitatory and inhibitory spinal V2 interneurons.
Recent Recommendation
Neuroligin-1 is required for normal expression of LTP and associative fear memory in the amygdala of adult animals.
Recent Recommendation
Functional significance of rare neuroligin 1 variants found in autism.
ASD
Recent Recommendation
Genome-wide identification of transcriptional targets of RORA reveals direct regulation of multiple genes associated with autism spectrum disorder.
Recent Recommendation
Neuroligin-1-dependent competition regulates cortical synaptogenesis and synapse number.
Recent Recommendation
Neuroligin-1 induces neurite outgrowth through interaction with neurexin-1 and activation of fibroblast growth factor receptor-1.

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN170R001 
 copy_number_gain 
  
  
 Familial 
 Maternal 
 Simplex 
 GEN170R002 
 missense_variant 
 c.2383C>T 
 p.His795Tyr 
 De novo 
 NA 
 Simplex 
 GEN170R003 
 copy_number_gain 
  
  
 Familial 
 Maternal 
 Simplex 
 GEN170R004 
 copy_number_gain 
  
  
 Familial 
 Paternal 
 Unknown 
 GEN170R005 
 missense_variant 
 c.958G>A 
 p.Val320Ile 
 De novo 
 NA 
 Multiplex 
 GEN170R006 
 missense_variant 
 c.418G>T 
 p.Asp140Tyr 
 Familial 
 Paternal 
 Simplex 
 GEN170R007 
 missense_variant 
 c.266C>T 
 p.Pro89Leu 
 Familial 
 Maternal 
 Multi-generational 
 GEN170R008 
 missense_variant 
  
 p.Leu269Pro 
 Familial 
 Paternal 
 Simplex 
 GEN170R009 
 missense_variant 
  
 p.Gly297Glu 
 Familial 
 Maternal 
 Simplex 
 GEN170R010 
 missense_variant 
 c.269C>T 
 p.Thr90Ile 
 Unknown 
  
 Unknown 

Common

Variant ID
Polymorphism
SNP ID
Allele Change
Residue Change
Population Origin
Population Stage
Author, Year
 GEN170C001 
 copy_number_gain 
  
  
  
 AGRE, ACC 
 Discovery 
 GEN170C002 
 intron_variant 
 rs6779753 
 c.494-62482T>G;c.554-55095T>G;c.494-55095T>G;c.37+59407T>G 
  
 1158 cases and 2520 controls in the Grady Trauma Project (30% male, mean age 40 13 years) 
 Discovery 
 GEN170C003 
 intron_variant 
 rs4894661 
 c.647-21390T>C;c.767-21390T>C;c.707-21390T>C;c.191-21390T>C;c.-296-21390T>C;c.-269-21390T>C 
  
 134 cases and 246 controls in the Drakenstein Child Health Study (all female, mean age 26.4 5.6 years) 
 Discovery 
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
3
Duplication
 1
 
3
Duplication
 1
 
3
Duplication
 2
 
3
Duplication
 1
 
3
Duplication
 1
 
3
Duplication
 2
 
3
Deletion-Duplication
 20
 
3
Deletion
 2
 
3
Duplication
 1
 

Model Summary

Neuroligins are required for proper synapse maturation and brain function, but not for the initial formation of synaptic contacts.

References

Type
Title
Author, Year
Primary
Neuroligins determine synapse maturation and function.
Additional
Altered neuroligin expression is involved in social deficits in a mouse model of the fragile X syndrome.
Additional
Neuroligin-1 deletion results in impaired spatial memory and increased repetitive behavior.
Additional
Input-specific synaptic plasticity in the amygdala is regulated by neuroligin-1 via postsynaptic NMDA receptors.
Additional
Shared synaptic pathophysiology in syndromic and nonsyndromic rodent models of autism.
Additional
Neuroligins Sculpt Cerebellar Purkinje-Cell Circuits by Differential Control of Distinct Classes of Synapses.
Additional
Functional significance of rare neuroligin 1 variants found in autism.

M_NLGN1_1_KO_ HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: A neo cassette inserted into the locus replaced the exon encompassing the translational start site at 546 bp.
Allele Type: Targeted (knock-out)
Strain of Origin: Not Specified
Genetic Background: Not Specified
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_NLGN1_2_TG_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Expression of an HA tagged construct of full length Nlgn1 under the thy1-promoter.
Allele Type: Targeted (Transgene)
Strain of Origin: Not Specified
Genetic Background: C57BL6J
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_NLGN1_3_TG_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Expression of an HA tagged construct of full length Nlgn1 under the thy1-promoter in Fmr1 knock-outs.
Allele Type: Targeted (Transgene)
Strain of Origin: Not Specified
Genetic Background: C57BL6J
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_NLGN1_4_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Mice with a null deletion of Nlgn1 (Song et al, 1999).
Allele Type: Targeted (knock-out)
Strain of Origin: Not Specified
Genetic Background: Not Specified
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_NLGN1_5_CKO_HM_NLGN2_NLGN3_CKO_HM_CB

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Triple conditional knockout mice with deletions in exon 7 of Nlgn1, exons 3-6 in Nlgn2 and exons 2-3 in Nlgn3 in Purkinje cells of the mature cerebellum by stereotactic injection of AAVs active Cre-recombinase (Cre) into the cerebellum of Nlgn1,2,3 floxed mice at P21
Allele Type: Conditional loss-of-function
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_NLGN1_5_CKO_HM_NLGN2_NLGN3_CKO_HM_PURKINJEN

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Triple conditional knockout mice with deletions in exon 7 of Nlgn1, exons 3-6 of Nlgn2 and exons 2-3 of Nlgn3 using L7-cre in Purkinje cells of the cerebellum
Allele Type: Conditional loss-of-function
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_NLGN1_6_CKO_HM_NLGN3_CKO_HM_PURKINJEN

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Double conditional knockout mice with deletions in exon 7 of neuroligin 1 and exons 2-3 of neuroligin 3 using L7-Cre, in Purkinje neurons of the cerebellum
Allele Type: Conditional loss-of-function
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_NLGN1_7_CKO_HM_PURKINJEN

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Conditional deletion of exon 7 of Nlgn1 using L7-cre in the Purkinje cells of the cerebellum
Allele Type: Conditional loss-of-function
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_NLGN1_8_KI_HM_P89L

Model Type: Genetic
Model Genotype: Homozygous
Mutation: KI mice with P89L substitution in exon3 of Nlgn1. CRISPR/Cas9 system was used to incorporate the P89L substitution, and a silent mutation at nucleotide 261 to delete a BsrBI restriction enzyme site to facilitate genotyping. The donor single-stranded oligonucleotide containing target mutations, target sgRNA, and Cas9 mRNA were injected in to the cytoplasm of fertilized eggs harvested from C57BL/6J mice. NLGN1 P89L KI mice were crossed with Thy1-YFP line H transgenic mice to examine spine number in the hippocampus CA1 slice. Homozygous mutants have Leucine as the 89th residue in both alleles.
Allele Type: Loss of function
Strain of Origin: C57BL/6J
Genetic Background: C57BL/6J
ES Cell Line: C57BL/6J
Mutant ES Cell Line: C57BL/6J
Model Source: Takumi Laboratory, RIKEN Brain Science Institute

M_NLGN1_9_KI_HT_P89L

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: KI mice with P89L substitution in exon3 of Nlgn1. CRISPR/Cas9 system was used to incorporate the P89L substitution, and a silent mutation at nucleotide 261 to delete a BsrBI restriction enzyme site to facilitate genotyping. The donor single-stranded oligonucleotide containing target mutations, target sgRNA, and Cas9 mRNA were injected in to the cytoplasm of fertilized eggs harvested from C57BL/6J mice. NLGN1 P89L KI mice were crossed with Thy1-YFP line H transgenic mice to examine spine number in the hippocampus CA1 slice. Heterozygous mutants have Leucine as the 89th residue in one allele and Proline in the other allele.
Allele Type: Loss of function
Strain of Origin: C57BL/6J
Genetic Background: C57BL/6J
ES Cell Line: C57BL/6J
Mutant ES Cell Line: C57BL/6J
Model Source: Takumi Laboratory, RIKEN Brain Science Institute

M_NLGN1_1_KO_ HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Synaptic plasticity3
Increased
Description: Increased STD-LTP induction in the thalamo-amygdala synapses after extra depolarization
Exp Paradigm: LTP induction by 80 presynaptic stimuli at 2 Hz to elicit EPSP in current clamp mode after extra depolarization
 Whole-cell patch clamp
 Unreported
Synaptic plasticity3
Decreased
Description: Decreased STD-LTP induced in the thalamo-amygdala synapses
Exp Paradigm: LTP induction by 80 presynaptic stimuli at 2 Hz to elicit EPSP in current clamp mode
 Whole-cell patch clamp
 Unreported
Voltage sensitivity of n-methyl d-aspartate (nmda) receptors3
Decreased
Description: Decreased amplitude of NMDAR-EPSCs at both positive and negative holding potentials
Exp Paradigm: Voltage clamp recordings after stimulation of internal capsule
 Whole-cell patch clamp
 Unreported
Synaptic neuroreceptor ratio (nmdar/ampar) dependent transmission3
Decreased
Description: Decreased NMDAR/AMPAR ratio at thalamo-amygdala synapse and cortical pathway
Exp Paradigm: whole-cell patch clamp
 Whole-cell patch clamp
 Unreported
Synaptic transmission1
Abnormal
Description: Abnormal Synaptic Transmission.
Exp Paradigm: Whole cell recordings
 Whole-cell patch clamp
 4 weeks
Pain or nociception2
Increased
Description: Increased sensitivity to heat
Exp Paradigm: Response to hotplate test at 52 degrees
 Hot plate test
 Unreported
Pain or nociception2
Decreased
Description: Decreased sensitivity to footshock
Exp Paradigm: Response to footshock test
 Foot shock test
 Unreported
Cued or contextual fear conditioning: memory of cue: short-term memory1
Decreased
Description: Decreased contextual and cued fear memory
Exp Paradigm: Contextual and repeated auditory cues before the conditioning electrical shocks.
 Fear conditioning test
 6-7 weeks
Protein expression level evidence2
Increased
Description: Increased expression levels of NL3, liprin, CSP, and munc-18 synaptic proteins in brain
Exp Paradigm: Pre/Post-Synaptic Protein Levels
 Western blot
 Unreported
Protein expression level evidence2
Decreased
Description: Decreased expression levels of alpha and beta neurexin
Exp Paradigm: Pre/Post-Synaptic Protein Levels
 Western blot
 Unreported
Anxiety2
 No change
 Elevated plus maze test
 Unreported
Anxiety2
 No change
 Light-dark exploration test
 Unreported
Anxiety1
 No change
 Open field test
 6-7 weeks
Anxiety2
 No change
 Open field test
 Unreported
Cued or contextual fear conditioning: memory of cue: short-term memory2
 No change
 Fear conditioning test
 Unreported
Protein expression level evidence2
 No change
 Western blot
 Unreported
General locomotor activity2
 No change
 Light-dark exploration test
 Unreported
General locomotor activity2
 No change
 Open field test
 Unreported
Motor coordination and balance2
 No change
 Accelerating rotarod test
 Unreported
Intrinsic membrane properties3
 No change
 Whole-cell patch clamp
 Unreported
Synaptic plasticity3
 No change
 Whole-cell patch clamp
 Unreported
Synaptic plasticity3
 No change
 Whole-cell patch clamp
 Unreported
Voltage sensitivity of n-methyl d-aspartate (nmda) receptors3
 No change
 Whole-cell patch clamp
 Unreported
Sensorimotor gating2
 No change
 Prepulse inhibition
 Unreported
Startle response: acoustic stimulus2
 No change
 Acoustic startle reflex 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_NLGN1_2_TG_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Synapse density1
Increased
Description: Increased numbers of excitatory synapses as indicated by puncta positive for PSD95 and Vglut
Exp Paradigm: Immunostaining analysis for PSD95 and Vglut
 Immunohistochemistry
 2.5-6 months
Social interaction1
Abnormal
Description: Abnormal social interaction demonstrated by decreased passive contact time but normal active contact time
Exp Paradigm: Direct social interaction task
 Reciprocal social interaction test
 2.5-6 months
Protein expression level evidence1
Increased
Description: Increased expression of Nlgn2 in cerebellum
Exp Paradigm: Protein Expression
 Immunohistochemistry
 2.5-6 months
Size/growth1
 No change
 General observations
 2.5-6 months
Object recognition memory1
 No change
 Novel object recognition test
 2.5-6 months
Spatial learning1
 No change
 Morris water maze test
 2.5-6 months
Protein expression level evidence1
 No change
 Immunohistochemistry
 2.5-6 months
General locomotor activity1
 No change
 Open field test
 2.5-6 months
Swimming ability1
 No change
 Swim test
 2.5-6 months
Synapse density1
 No change
 Immunohistochemistry
 2.5-6 months
Aggression1
 No change
 Resident-intruder test
 2.5-6 months
Social interaction1
 No change
 Resident-intruder test
 2.5-6 months
Social interaction1
 No change
 Reciprocal social interaction test
 2.5-6 months
 Not Reported: Circadian sleep/wake cycle, Communications, Emotion, Immune response, Maternal behavior, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory

M_NLGN1_3_TG_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Synapse density1
Increased
Description: Increased numbers of inhibitory synapses as indicated by puncta positive for gephyrin and VGAT
Exp Paradigm: Immunostaining analysis for gephyrin and VGAT
 Immunohistochemistry
 2.5-6 months
Synapse density1
Increased
Description: Increased numbers of excitatory synapses as indicated by puncta positive for PSD95 and Vglut
Exp Paradigm: Immunostaining analysis for PSD95 and Vglut
 Immunohistochemistry
 2.5-6 months
Protein expression level evidence1
Increased
Description: Increased expression of Nlgn1 in hippocampus
Exp Paradigm: Protein Expression
 Immunohistochemistry
 2.5-6 months
Mortality/lethality1
 No change
 General observations
 2.5-6 months
Reproductive system development1
 No change
 General observations
 2.5-6 months
Size/growth1
 No change
 General observations
 2.5-6 months
Object recognition memory1
 No change
 Novel object recognition test
 2.5-6 months
Spatial learning1
 No change
 Morris water maze test
 2.5-6 months
General locomotor activity1
 No change
 Open field test
 2.5-6 months
Swimming ability1
 No change
 Swim test
 2.5-6 months
Aggression1
 No change
 Resident-intruder test
 2.5-6 months
Social interaction1
 No change
 Reciprocal social interaction test
 2.5-6 months
Social interaction1
 No change
 Resident-intruder test
 2.5-6 months
Social interaction1
 No change
 Reciprocal social interaction test
 2.5-6 months
 Not Reported: Circadian sleep/wake cycle, Communications, Emotion, Immune response, Maternal behavior, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory

M_NLGN1_4_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Protein expression level evidence1
 No change
 Western blot
 2-3 months
Neuroreceptor levels: glutamate receptors: nmda receptors1
 No change
 Quantitative pcr (qrt-pcr)
 2-3 months
Neuroreceptor levels: glutamate receptors: nmda receptors1
 No change
 Western blot
 2-3 months
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Motor phenotype, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_NLGN1_5_CKO_HM_NLGN2_NLGN3_CKO_HM_CB

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Miniature post synaptic current frequency: inhibitory1
Decreased
Description: Mutants show a large decrease in IPSC frequency in Basket cells and Stellate cells, compared to controls. Mutants show no change in IPSCs induced by direct puffing of GABA onto Purkinje cells, compared to controls.
Exp Paradigm: Monitored IPSCs from basket-cell and stellate cell synapses that are formed on proximal dendrites and the soma of Purkinje cells.
 Whole-cell patch clamp
 P21-25
Miniature post synaptic current amplitude: inhibitory1
Decreased
Description: Mutants show a large decrease in IPSC amplitude in Purkinje cells, basket cells and stellate cells, compared to controls. Mutants show no change in paired-pulse ratio in Purkinje cells compared to contols, suggesting that the decrease in IPSC amplitude is caused by a postsynaptic change. Mutants show no change in IPSCs induced by direct puffing of GABA onto Purkinje cells, compared to controls.
Exp Paradigm: Monitored IPSCs from basket-cell synapses that are formed on proximal dendrites and the soma of Purkinje cells.
 Whole-cell patch clamp
 P21-25
Spontaneous post synaptic events: inhibitory currents1
Decreased
Description: Mutants show decrease in spontaneous mIPSC frequency in basket and stellate cells comapred to controls.
Exp Paradigm: Monitored IPSCs from basket-cell and stellate cell synapses that are formed on proximal dendrites and the soma of Purkinje cells.
 Whole-cell patch clamp
 P21-25
Miniature post synaptic current amplitude: excitatory1
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
 P21-25
Spontaneous post synaptic event amplitude: inhibitory currents1
Decreased
Description: Mutants show decrease in spontaneous mIPSC amplitude in basket and stellate cells comapred to controls.
Exp Paradigm: Monitored IPSCs from basket-cell and stellate cell synapses that are formed on proximal dendrites and the soma of Purkinje cells.
 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, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_NLGN1_5_CKO_HM_NLGN2_NLGN3_CKO_HM_PURKINJEN

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Synapse density1
Decreased
Description: Mutants show a large decrease in the number of climbing fiber synapses (vGluT2) on distal Purkinje cells dendrites and a small decrease in the number of climbing fiber synapses on proximal Purkinje cell dendrites, compared to controls. Mutants show decreased NL-2 synapses on Purkinje cells, compared to controls.
Exp Paradigm: vGluT2 was used to label climbing-fiber synapses.
 Histology
 Unreported
Synaptic morphology1
Increased
Description: Mutants show increase in basket cell synapse size compared to controls.
 Histology
 Unreported
Synaptic morphology1
Increased
Description: Mutants show an increase in GAD65 positive inhibitory synapse size on Purkinje cells compared to controls.
Exp Paradigm: Staining of cerebellar cortex for the vesicular GABA transporter (vGAT) and and a marker of GABAergic presynaptic terminals (GAD65) were used.
 Histology
 Unreported
Synaptic morphology1
Decreased
Description: Mutants show a decrease in the size of climbing-fiber synapses on both distal and proximal Purkinje cell dendrites, compared to controls.
Exp Paradigm: vGluT2 was used to label climbing-fiber synapses.
 Histology
 Unreported
Synaptic morphology: active zone1
Decreased
Description: Mutants show an decrease in bouton size of climbing fiber synapses on Purkinje cells compared to controls.
 Electron microscopy
 Unreported
Miniature post synaptic current frequency: inhibitory1
Decreased
Description: Mutants show a large decrease in IPSC frequency in Basket cells and Stellate cells, compared to controls. Mutants show no change in IPSCs induced by direct puffing of GABA onto Purkinje cells, compared to controls.
Exp Paradigm: Monitored IPSCs from basket-cell and stellate cell synapses that are formed on proximal dendrites and the soma of Purkinje cells.
 Whole-cell patch clamp
 P21-25
Spontaneous post synaptic events: inhibitory currents1
Decreased
Description: Mutants show decrease in spontaneous mIPSC frequency in basket and stellate cells comapred to controls.
Exp Paradigm: Monitored IPSCs from basket-cell and stellate cell synapses that are formed on proximal dendrites and the soma of Purkinje cells.
 Whole-cell patch clamp
 P21-25
Miniature post synaptic current amplitude: inhibitory1
Decreased
Description: Mutants show a large decrease in IPSC amplitude in Purkinje cells, Basket cells and Stellate cells, compared to controls. Mutants show no change in paired-pulse ratio in Purkinje cells compared to contols, suggesting that the decrease in IPSC amplitude is caused by a postsynaptic change. Mutants show no change in IPSCs induced by direct puffing of GABA onto Purkinje cells, compared to controls.
Exp Paradigm: Monitored IPSCs from basket-cell synapses that are formed on proximal dendrites and the soma of Purkinje cells.
 Whole-cell patch clamp
 P21-25
Spontaneous post synaptic event amplitude: inhibitory currents1
Decreased
Description: Mutants show decrease in spontaneous mIPSC amplitude in basket and stellate cells comapred to controls.
Exp Paradigm: Monitored IPSCs from basket-cell and stellate cell synapses that are formed on proximal dendrites and the soma of Purkinje cells.
 Whole-cell patch clamp
 P21-25
Miniature post synaptic current amplitude: excitatory1
Decreased
Description: Mutants show decreased amplitude of climbing-fiber excitatory postsynaptic currents compared to controls. Mutants show no change in amplitude of parallel fiber excitatory post synaptic currents comapred to controls.
Exp Paradigm: Climbing fibers were identified by their characteristic all-or-none response.
 Whole-cell current clamp
 P21-25, Adult
Neurotransmitter release1
Decreased
Description: Mutants show a decrease in quantal release frequency but no change in quantal amplitude or quantal decay time compared to contols.
Exp Paradigm: Measurment of strontium mediated delayed quantal release events that trail evoked climbing-fiber synapse EPSCs.
 Whole-cell patch clamp
 P21-25
Targeted expression1
Decreased
Description: Mutants show decreased expression of Nlgn1,2 and 3 compared to controls. Cre immunostaining revealed Purkinje cell-specific Cre activity in L7- cre transgenic mice.
Exp Paradigm: Protein levels were measured by immunoblotting using fluorescently labeled secondary antibodies and LICOR detection.
 Western blot
 Unreported, P10, P14
Protein expression level evidence1
Decreased
Description: Mutants show decreased protein levels of PICK1 and alpha neurexin in the cerebellum compared to controls.
Exp Paradigm: Protein levels were measured by immunoblotting using fluorescently labeled secondary antibodies and LICOR detection.
 Western blot
 Unreported, P10, P14
General characteristics1
 No change
 General observations
 Unreported
Mortality/lethality1
 No change
 General observations
 4 months
Size/growth1
 No change
 Body weight measurement
 3, 8 weeks
Protein expression level evidence1
 No change
 Western blot
 Unreported, P10, P14
Cerebellar morphology1
 No change
 Histology
 Unreported
Cerebellar morphology: granule cell layer thickness1
 No change
 Histology
 Unreported
Cerebellar morphology: molecular layer thickness1
 No change
 Histology
 Unreported
Dendritic architecture: spine turnover1
 No change
 Whole-cell current clamp
 P21-25, 2 months
Neuronal number: interneurons1
 No change
 Histology
 P21-25, Adult
Synapse density1
 No change
 Histology
 Unreported
Synapse density: inhibitory1
 No change
 Histology
 Unreported
Synaptic morphology1
 No change
 Histology
 Unreported
Decay kinetics of miniature post synaptic currents1
 No change
 Whole-cell current clamp
 P21-25
Intrinsic membrane properties1
 No change
 Whole-cell patch clamp
 P21-25
Miniature post synaptic current frequency: excitatory1
 No change
 Whole-cell current clamp
 P21-25, Adult
Presynaptic function: paired-pulse facilitation1
 No change
 Whole-cell current clamp
 P21-25, 2 months
Synaptic plasticity: cerebellar ltd1
 No change
 Whole-cell patch clamp
 P21-25
 Not Reported: Circadian sleep/wake cycle, Communications, Emotion, Immune response, Learning & memory, Maternal behavior, Motor phenotype, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_NLGN1_6_CKO_HM_NLGN3_CKO_HM_PURKINJEN

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Synaptic morphology1
Decreased
Description: Mutants show a decrease in the size of climbing-fiber synapses on both distal and proximal Purkinje cell dendrites, compared to controls.
Exp Paradigm: vGluT1 and cGluT2 was used to label parallel-fiber and climbing-fiber synapses.
 Histology
 1.2 months
Synapse density1
Decreased
Description: Mutants show a uniform decrease in the number of climbing fiber synapses (vGluT2) on distal and proximal Purkinje cells dendrites, compared to controls.
Exp Paradigm: vGluT2 was used to label climbing-fiber synapses.
 Histology
 1.2 months
Miniature post synaptic current amplitude: excitatory1
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 expression1
Decreased
Description: Mutants show decreased expression of Nlgn1 and Nlgn3, compared to controls.
Exp Paradigm: Calbindin and actin are used as loading controls.
 Western blot
 Unreported
Size/growth1
 No change
 Body weight measurement
 10 weeks
Protein expression level evidence1
 No change
 Western blot
 Unreported
Dendritic architecture: spine turnover1
 No change
 Whole-cell current clamp
 P21-25
Intrinsic membrane properties1
 No change
 Whole-cell patch clamp
 P21-25
Miniature post synaptic current amplitude: inhibitory1
 No change
 Whole-cell patch clamp
 P21-25
Miniature post synaptic current frequency: inhibitory1
 No change
 Whole-cell patch clamp
 P21-25
Presynaptic function: paired-pulse facilitation1
 No change
 Whole-cell current clamp
 1.2 months
Spontaneous post synaptic event amplitude: inhibitory currents1
 No change
 Whole-cell patch clamp
 P21-25
Spontaneous post synaptic events: inhibitory currents1
 No change
 Whole-cell patch clamp
 P21-25
 Not Reported: Circadian sleep/wake cycle, Communications, Emotion, Immune response, Learning & memory, Maternal behavior, Motor phenotype, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior

M_NLGN1_7_CKO_HM_PURKINJEN

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Miniature post synaptic current amplitude: excitatory1
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 expression1
Decreased
Description: Mutants show decreased expression of Nlgn1 compared to controls.
Exp Paradigm: Calbindin and actin are used as loading controls.
 Western blot
 Unreported
Protein expression level evidence1
 No change
 Western blot
 Unreported
Intrinsic membrane properties1
 No change
 Whole-cell patch clamp
 P21-25
Miniature post synaptic current amplitude: inhibitory1
 No change
 Whole-cell patch clamp
 P21-25
Miniature post synaptic current frequency: inhibitory1
 No change
 Whole-cell patch clamp
 P21-25
Presynaptic function: paired-pulse facilitation1
 No change
 Whole-cell current clamp
 1.2 months
Spontaneous post synaptic event amplitude: inhibitory currents1
 No change
 Whole-cell patch clamp
 P21-25
Spontaneous post synaptic events: inhibitory currents1
 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_NLGN1_8_KI_HM_P89L

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Social dominance1
Decreased
Description: Mutants retreated more frequently than controls.
 Tube test of social dominance
 Not specified
Spatial working memory1
Decreased
Description: Mutant mice showed a mild but significant delay of learning both in distance traveled and latency to reach the target during the training phase, compared to controls.
 Morris water maze test
 Not specified
Spatial reference memory1
Decreased
Description: Mutants show no change in the time spent in the target quadrant versus the opposite or adjacent quadrants during the probe trial phase when the platform is removed, compared to controls.
 Morris water maze test
 Not specified
Targeted expression1
Decreased
Description: Mutants show decrease in the levels of Nlgn1 protein compared to controls, including in the cortical synaptosomal fraction.
 Western blot
 Not specified
Ultrasonic vocalization: isolation induced1
 No change
 Monitoring ultrasonic vocalizations
 1 week
General characteristics1
 No change
 General observations
 Not specified
Anxiety1
 No change
 Elevated plus maze test
 Not specified
Targeted expression1
 No change
 Quantitative pcr (qrt-pcr)
 Not specified
General locomotor activity: ambulatory activity1
 No change
 Open field test
 Not specified
Dendritic architecture: spine density1
 No change
 Immunohistochemistry
 Not specified
Reproductive function1
 No change
 General observations
 Adult
Repetitive digging1
 No change
 Marble-burying test
 Not specified
Self grooming: perseveration1
 No change
 Grooming behavior assessments
 Not specified
Social approach1
 No change
 Three-chamber social approach test
 Not specified
Social interaction1
 No change
 Reciprocal social interaction test
 Not specified
 Not Reported: Circadian sleep/wake cycle, Immune response, Maternal behavior, Neurophysiology, Physiological parameters, Seizure, Sensory

M_NLGN1_9_KI_HT_P89L

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Social approach1
Decreased
Description: Mutants show no significant difference in time spent in the inanimate object chamber versus the chamber with the unfamiliar mouse whereas wildtype controls spend more time with the unfamiliar mouse than the inanimate object.
 Three-chamber social approach test
 Not specified
Social interaction1
Decreased
Description: Mutants show significant decrease in time spent around a caged male mouse in the center of the open field, compared to controls.
 Reciprocal social interaction test
 Not specified
Social dominance1
Decreased
Description: Mutants retreated more frequently than controls.
 Tube test of social dominance
 Not specified
Spatial reference memory1
Decreased
Description: Mutants show increased latency to reach the hidden platform and during the probe test when the platform was removed mutants spent less time in the target quadrant compared to controls.
 Morris water maze test
 Not specified
Targeted expression1
Decreased
Description: Mutants show decrease in the levels of Nlgn1 protein compared to controls, including in the cortical synaptosomal fraction.
 Western blot
 Not specified
Ultrasonic vocalization: interaction induced: opposite sex stimulus1
 No change
 Monitoring ultrasonic vocalizations
 4 months
Ultrasonic vocalization: isolation induced1
 No change
 Monitoring ultrasonic vocalizations
 1 week
General characteristics1
 No change
 General observations
 Not specified
Anxiety1
 No change
 Elevated plus maze test
 Not specified
Object recognition memory1
 No change
 Novel object recognition test
 Not specified
Olfactory learning and memory1
 No change
 Olfactory habituation-dishabituation test
 Not specified
Spatial working memory1
 No change
 Morris water maze test
 Not specified
Targeted expression1
 No change
 Quantitative pcr (qrt-pcr)
 Not specified
General locomotor activity: ambulatory activity1
 No change
 Open field test
 Not specified
Dendritic architecture: spine density1
 No change
 Immunohistochemistry
 Not specified
Reproductive function1
 No change
 General observations
 Adult
Repetitive digging1
 No change
 Marble-burying test
 Not specified
Self grooming: perseveration1
 No change
 Grooming behavior assessments
 Not specified
Sensorimotor gating1
 No change
 Acoustic startle reflex test
 Not specified
 Not Reported: Circadian sleep/wake cycle, Immune response, Maternal behavior, Neurophysiology, Physiological parameters, Seizure


Interactor Symbol Interactor Name Interactor Organism Entrez ID Uniprot ID Interaction Type Evidence Reference
B3GAT3 Galactosylgalactosylxylosylprotein 3-beta-glucuronosyltransferase 3 26229 O94766 IP; LC-MS/MS
Huttlin EL , et al. 2015
CDKL5 cyclin-dependent kinase-like 5 6792 O76039 IP/WB; in vitro kinase assay
Ricciardi S , et al. 2012
NLGN3 neuroligin 3 54413 D3DVV1 IP; LC-MS/MS
Huttlin EL , et al. 2015
Fmr1 fragile X mental retardation 1 14265 P35922 IP; qRT-PCR
Dahlhaus R and El-Husseini A 2009
Nlgn3 neuroligin 3 245537 Q8BYM5 IP/WB
Budreck EC and Scheiffele P 2007
Nrxn1 neurexin 1 18189 Q9CS84 IP/WB; Cell aggregation assay; Co-localization
Singh SK , et al. 2016
NRXN1 neurexin 1 18189 Q9CS84 IP/WB; IP; LC-MS/MS
Traunmller L , et al. 2016
Nrxn2 neurexin II 18190 E9Q7X7 IP/WB
Singh SK , et al. 2016
Sipa1l1 signal-induced proliferation-associated 1 like 1 217692 Q8C0T5 IP/WB
Liu A , et al. 2016
SPARCL1 SPARC-like 1 13602 P70663 IP/WB; Cell surface binding assay
Singh SK , et al. 2016
Thbs1 thrombospondin 1 21825 P35441 IP/WB; Solid phase binding assay
Xu J , et al. 2009
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; Surface plasmon resonance (SPR); Affinity chromatography
Irie M , et al. 1997
MECP2 methyl CpG binding protein 2 (Rett syndrome) 29386 Q00566 IP/WB; ChIP
Bie B , et al. 2014
NRXN1 neurexin 1 60391 Q63373 IP; LC-MS/MS; Co-localization
Savas JN , et al. 2015
NRXN1 neurexin 1 60391 Q63373 Affinity chromatography; IP/WB
Ichtchenko K , et al. 1995
NRXN1 neurexin 1 60391 Q63373 Affinity chromatography
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

HELP
Copyright © 2017 MindSpec, Inc.