B6;129S-Nlgn2^tm1.1Gchn/J

Stock number: 031963
Product name: NL2 R215H
Research areas: Neurobiology Research, Research Tools

Description

An Arg215His (R215H) loss-of-function point mutation in the human neuroligin 2 gene has been identified in schizophrenia patients. These NL2 R215H mice carry a corresponding R215H point mutation in the mouse Nlgn2 gene in addition to loxP sites flanking exons 4-7.

Detailed description

The Nlgn2 (neuroligin 2) gene encodes a cell adhesion molecule critical for GABAergic synapse formation and function. An Arg215His (R215H) loss-of-function point mutation in the human gene has been identified in schizophrenia patients. These mice carry a corresponding R215H point mutation in the mouse Nlgn2 gene in addition to loxP sites flanking exons 4-7.

Mice homozygous for the R215H mutation (and retaining the floxed exons) show a significant loss of NLGN2 protein, reduced GABAergic transmission, and impaired hippocampal activation. They also display anxiety-like behaviors, impaired pre-pulse inhibition (PPI), cognition deficits and abnormal stress responses, recapitulating several key aspects of schizophrenia-like behavior. Males and females perform similarly.

NL2 R215H heterozygotes and homozygotes are viable and fertile and do not exhibit premature mortality. Homozygotes are born at normal Mendelian ratios.

Cre-mediated excision of floxed exons 4-7 has not been tested (May, 2018).

Development

An Arg215His (R215H amino acid; G644A nucleotide) mutation was introduced to exon 4 of the mouse Nlgn2 gene via homologous recombination in (129SvEv x C57BL/6J)F1-derived embryonic stem cells. A loxP site and an FRT-flanked PGK-neomycin cassette (in reverse transcriptional orientation) was placed in intron 3 along with a loxP site in intron 7 (thus flanking exons 4-7 with loxP sites). Resultant chimeric animals were crossed with ROSA26-Flpe mice (Stock No. 003946 animals that the donating lab subsequently backcrossed to C57BL/6J for more than 10 generations) to excise the FRT-flanked neomycin cassette. The mutation was maintained on a C57BL/6J-129 mixed genetic background by the donating laboratory.

Allele

Symbol: Nlgn2^tm1.1Gchn
Name: targeted mutation 1.1, Gong Chen
MGI accession ID: MGI:6158645
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); Humanized sequence
Synonyms: Nlgn2^R215H
Marker symbol: Nlgn2
Marker name: neuroligin 2
Marker synonyms: MGC:67386; NL2; NLG2
Chromosome: 11
Strain of origin: (129S/SvEv x C57BL/6J)F1
Molecular note: A loxP site and an FRT-flanked PGK-neomycin cassette (in reverse transcriptional orientation) are placed in intron 3 along with a loxP site in intron 7 (thus flanking exons 4-7 with loxP sites). In addition, an Arg215His (R215H amino acid; G644A nucleotide) mutation is introduced to exon 4 of the gene. Flp-mediated recombination removed the FRT-flanked neo cassette. The Arg215His (R215H) loss-of-function point mutation in the human gene has been identified in schizophrenia patients.