B6.129S6(Cg)-Wwc1^tm1.1Rlh/J

Stock number: 024415
Product name: KIBRA knockout
Research areas: Neurobiology Research

Description

This strain carries a targeted knockout of the mouse Wwc1 (KIBRA) gene and is useful in studies of synaptic plasticity, learning, and memory.

Detailed description

Mutations in the WWC1 (WW, C2 and coiled-coil domain containing 1; also called KIBRA) gene have been associated with human memory performance.

This strain carries a targeted knockout of the mouse Wwc1 gene. Western blot analysis confirmed the absence of protein expression in the brain. Adult homozygous mice demonstrate impaired long-term depression and long-term potentiation at hippocampal Schaffer collateral-CA1 synapses. They also show severe deficits in contextual fear learning and memory. WWC1/KIBRA directly binds PICK1 in vitro and in vivo and interacts with GluA1 (GRIA1), GluA2 (GRIA2), and several other synaptic proteins in an in vivo protein complex. Evidence suggests that the gene plays and important role in regulating AMPAR (α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor) trafficking underlying synaptic plasticity and learning.

Mice carrying the floxed (pre-cre) version of this knock-out allele are available as Stock No. 037474.

Development

A loxP site was introduced upstream of exon 4 and an FRT-flanked PGK-neomycin cassette followed by a loxP site was placed downstream of exon 5. The targeting vector was introduced to 129S6/SvEvTac-derived MC1 embryonic stem (ES) cells. Resultant germline mice were crossed with a CMV-Cre strain on a C57BL/6 background to excise the floxed region, resulting in an out-of-frame mutation. This strain was backcrossed to C57BL/6 for 10 generations by the donating laboratory.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.

Allele

Symbol: Wwc1^tm1.1Rlh
Name: targeted mutation 1.1, Richard L Huganir
MGI accession ID: MGI:5301655
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: Kibra knockout
Marker symbol: Wwc1
Marker name: WW, C2 and coiled-coil domain containing 1
Marker synonyms: HBEBP3; HBEBP36; KIBRA; MEMRYQTL; MGC:47054; PPP1R168; RGD1308329
Chromosome: 11
Strain of origin: 129S6/SvEvTac
Molecular note: A loxP site was inserted upstream of exon 4. An FRT-flanked neo cassette with a 3' loxP site was inserted downstream of exon 5. Cre-mediated recombination removed the exon 4, exon 5, and the neo cassette. Western blot analysis confirmed the absence of protein expression in the brain.