B6;129-Nlgn3^tm1Sud/J

Stock number: 008475
Product name: AU4
Research areas: Neurobiology Research, Research Tools

Description

These mice carry an R451C mutation in exon 7 of the Nlgn3 (neuroligin 3) gene. mRNA is detected by real-time PCR analysis of brain from homozygous animals. Mutant mice exhibit enhancements in inhibitory synaptic transmission as well as spacial learning and memory, but show deficits in social interaction. This mutant mouse strain may be useful in studies of the pathophysiology of autism. Exon 7 is additionally flanked by loxP sites. When used in conjunction with a Cre recombinase-expressing strain, this strain is useful in generating tissue-specific mutants of the floxed allele. Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical abnormalities.

Detailed description

These mice carry an R451C mutation in exon 7 of the gene. mRNA is detected by real-time PCR analysis of brain from homozygous animals. Mutant mice exhibit enhancements in inhibitory synaptic transmission as well as spacial learning and memory, but show deficits in social interaction. This mutant mouse strain may be useful in studies of the pathophysiology of autism. Exon 7 is additionally flanked by loxP sites. When used in conjunction with a Cre recombinase-expressing strain, this strain is useful in generating tissue-specific mutants of the floxed allele. Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical abnormalities.

Development

Residue 451 of exon 7 (encoding arginine) was mutated to create a cysteine substitution (R451C). The same exon was flanked by loxP sites. A neomycin-resistant cassette flanked by frt sites was inserted in intron 7. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1- Kitl⁺-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to the same for three to nine generations. The neomycin cassette was removed through crosses with a Flp strain (background not specified).

Allele

Symbol: Nlgn3^tm1Sud
Name: targeted mutation 1, Thomas C Sudhof
MGI accession ID: MGI:3758949
Generation method: Targeted
Attributes: Humanized sequence
Marker symbol: Nlgn3
Marker name: neuroligin 3
Chromosome: X
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Molecular note: Exon 7 was replaced with an exon 7 carrying an arginine to cysteine amino acid substitution at position 451 (R451C). A neo cassette used as a selectable marker was removed via flip-mediated recombination leaving a floxed exon 7 carrying the mutation. The R451C substitution in the extracellular esterase-homology domain that results in increased endoplasmic reticulum retention in humans with autism spectrum disorder. PCR was used to confirm the insertion. Western blot analysis reveal a decrease in protein expression to 10% of wild-type levels. Authors state that this mutation is likely to cause a gain-of-function mutation.