Nlgn2(-/-) mice displayed reduced exploratory activity, impaired rotarod performance, and delays on several developmental milestones, whereas Nlgn2(-/-) pups isolated from mother and littermates emitted fewer ultrasonic vocalizations and spent less time calling than Nlgn2(+/+) littermate controls (Wohr et al., 2013).
Molecular Function
Transmembrane scaffolding protein involved in cell-cell interactions via its interactions with neurexin family members. Plays a role in synapse function and synaptic signal transmission, especially via gamma-aminobutyric acid receptors (GABA(A) receptors), by recruiting and clustering synaptic proteins. Modulates signaling by inhibitory synapses, and thereby plays a role in controlling the ratio of signaling by excitatory and inhibitory synapses and information processing.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Developmental delays and reduced pup ultrasonic vocalizations but normal sociability in mice lacking the postsynaptic cell adhesion protein neuroli...
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Exon sequences covering the translational start site and at least 380 bp of 5' coding sequence were deleted by homologous recombination.
Allele Type: Targeted (Knock Out)
Strain of Origin: Not specified
Genetic Background: C57BL/6NCr1, 129S6/SvEvTac, 129S2/SvPasCr1f
ES Cell Line: Not specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Exon sequences covering the translational start site and at least 380 bp of 5' coding sequence were deleted by homologous recombination.
Allele Type: Targeted (Knock Out)
Strain of Origin: Not specified
Genetic Background: C57BL/6NCr1, 129S6/SvEvTac, 129S2/SvPasCr1f
ES Cell Line: Not specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional deletion of exons 3 - 6 of Nlgn2 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
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Double conditional knockout mice with deletions in exon 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
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
The Nlgn2 knockout was constructed by crossing mice with an Nlgn2-flox construct (MGI:5567078), in which exons 3 through 5 are flanked by loxP sites, to mice carrying a constitutively expressed Cre transgene, EIIa-Cre (MGI:2137691), resulting in deletion of exons 3-5 of the Nlgn2 floxed allele. The knockout carries two copies of the Nlgn2-flox construct.
Allele Type: Knockout
Strain of Origin: C57BL/6NTac; FVB/N
Genetic Background: C57BL/6J
ES Cell Line: Not specified
Mutant ES Cell Line: Model Source: Jackson Laboratory
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
The Nlgn2 knockout was constructed by crossing mice with an Nlgn2-flox construct (MGI:5567078), in which exons 3 through 5 are flanked by loxP sites, to mice carrying a constitutively expressed Cre transgene, EIIa-Cre (MGI:2137691), resulting in deletion of exons 3-5 of the Nlgn2 floxed allele. The heterozygote carries one copy of the Nlgn2-flox construct.
Allele Type: Knockout
Strain of Origin: C57BL/6NTac; FVB/N
Genetic Background: C57BL/6J
ES Cell Line: Not specified
Mutant ES Cell Line: Model Source: Jackson Laboratory
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
The Nlgn2 Avil conditional knockout was constructed by crossing mice with an Nlgn2-flox construct (MGI:5567078), in which exons 3 through 5 are flanked by loxP sites, to mice carrying Avil-Cre (MGI:4459942), where cre-IRES-EGFP was knocked into exon 2 of the Avil locus to achieve cre expression specifically within sensory neurons.
Allele Type: Conditional knockout
Strain of Origin: C57BL/6NTac; 129P2/OlaHsd
Genetic Background: C57BL/6J, 129/SvEv, CD1
ES Cell Line: Not specified
Mutant ES Cell Line: Model Source: Jackson Laboratory
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
The Nlgn2 Cdx2 conditional knockout was constructed by crossing mice with an Nlgn2-flox construct (MGI:5567078), in which exons 3 through 5 are flanked by loxP sites, to mice carrying Cdx2-Cre (MGI:3696953), a transgene designed with a 9.5 kb promoter fragment from the human caudal type homeo box 2 (CDX2) gene, a Cre recombinase gene with nuclear localization signal, and a bovine growth hormone polyadenylation cassette. The result is to conditionally delete Nlgn2 in all cells caudal to cervical level 2 of the spinal cord.
Allele Type: Conditional knockout
Strain of Origin: C57BL/6NTac; (C57BL/6J x SJL/J)
Genetic Background: C57BL/6J, 129/SvEv, CD1
ES Cell Line: Not specified
Mutant ES Cell Line: Model Source: Jackson Laboratory
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
The Nlgn2 Lbx1 conditional knockout was constructed by crossing mice with an Nlgn2-flox construct (MGI:5567078), in which exons 3 through 5 are flanked by loxP sites, to mice carrying Lbx1-Cre (MGI:3710149), where cre cDNA replaced exon 1 in the Lbx1 gene. The result is Nlgn2 deletion in 95% of all neurons in the low-threshold mechanoreceptor-recipient zone (LTMR-RZ) of the dorsal horn.
Allele Type: Conditional knockout
Strain of Origin: C57BL/6NTac; Not specified
Genetic Background: C57BL/6J, 129/SvEv, CD1
ES Cell Line: Not specified
Mutant ES Cell Line: Model Source: Jackson Laboratory
Description: Decreased locomotor activity indicated by lower total entries into both chambers
Exp Paradigm: Sociability three chambered test; elevated plus maze test-three-chamber social approach test: habituation
Description: Decreased locomotor activity indicated by lower total entries into both chambers
Exp Paradigm: Sociability three chambered test; elevated plus maze test- elevated plus maze test
Description: Decreased exploratory activity indicated by reduced total distance, horizontal activity, time in center of arena, and vertical activity
Exp Paradigm: Open field test
Description: Abnormal ultrasonic vocalizations as indicated by reduced call rate, and calling time; no change in latency to start calls, duration of calls, peak frequency & amplitude of calls
Exp Paradigm: Ultrasonic vocalizations in isolated pups
Description: Abnormal ultrasonic vocalization time course with no increase in call numbers over time
Exp Paradigm: Ultrasonic vocalizations in isolated pups time course during 5 minute isolation period
Description: Abnormal delayed developmental trajectory in body length, tail length, eye opening, and incisor eruption
Exp Paradigm: General observations
Description: Increased anxiety indicated by fewer transitions between light and dark chambers and less time spent in dark chamber
Exp Paradigm: Light/dark exploration task
Description: Abnormal ultrasonic vocalization time course with no increase in call numbers over time
Exp Paradigm: Ultrasonic vocalizations in isolated pups time course during 5 minute isolation period
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.
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.
Exp Paradigm: Monitored ipscs from basket-cell synapses that are formed on proximal dendrites and the soma of purkinje cells.
Miniature post synaptic current amplitude: excitatory1
Increased
Description: Mutants show increased amplitude of climbing-fiber excitatory postsynaptic currents compared to controls.
Exp Paradigm: Climbing fibers were identified by their characteristic all-or-none response.
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.
Description: Mutants show a slight decrease in the number of climbing fiber synapses (vglut2) on purkinje cells, compared to controls.
Exp Paradigm: Vglut2 was used to label climbing-fiber synapses.
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.
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.
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.
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.
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.
Description: Mutants show decreased expression of nlgn2 and nlgn3 compared to controls.
Exp Paradigm: Calbindin and actin are used as loading controls.
Description: Nlgn2 knockout mice do not show Nlgn2 expression in Nefh-positive (large diameter neurons) and Mrgprd (small diameter neurons) in dorsal root ganglia.
Exp Paradigm: Nefh, Mrgprd, Nlgn2
Description: Nlgn2 heterozygous mice exhibit enhanced sensitivity to back hairy skin stimulation, as measured by tactile prepulse inhibition (PPI) of an acoustic startle response.
Exp Paradigm: 0.9-psi air puff preceded 120 dB acoustic startle pulse,delivered at variable interstimulus intervals
Description: Avil-Cre Nlgn2 conditional knockout mice do not show Nlgn2 expression in Nefh-positive (large diameter neurons) and Mrgprd (small diameter neurons) in dorsal root ganglia.
Exp Paradigm: Nefh, Mrgprd, Nlgn2
Description: Cdx2-Cre Nlgn2 conditional knockout mice exhibit enhanced sensitivity to back hairy skin stimulation, as measured by tactile prepulse inhibition (PPI) of an acoustic startle response.
Description: Lbx1-Cre Nlgn2 conditional knockout mice exhibit enhanced sensitivity to back hairy skin stimulation, as measured by tactile prepulse inhibition (PPI) of an acoustic startle response.
