B6.129P2-Msh2^tm1Mak/Mmjax

Stock number: 029904
Product name: MSH2^-
Research areas: Cancer Research, Research Tools

Description

A percentage of Msh2 (mutS homolog 2) knock-out mice develop lymphoid tumors containing microsatellite instabilities by two months of age. These mice may be useful for studies of the pathogenesis of cancer and as a screen for carcinogenic and anti-cancer agents.

Detailed description

The Msh2 (mutS homolog 2) gene encodes a homolog of the E. coli mismatch repair gene mutS. Mutations in Msh2 are associated with hereditary nonpolyposis colon cancer (HNPCC). Mice homozygous for the knockout allele are viable and fertile. Beginning at two months of age, some MSH2^- mice develop lymphoid tumors containing microsatellite instabilities. Five the six mice diagnosed with lymphoblastic lymphoma exhibit widely disseminated lymphoma in the spleen, liver and thymus. Mice that develop lymphomas die by 5 months of age. These mice may be useful for studies of the pathogenesis of cancer and as a screen for carcinogenic and anti-cancer agents.

Development

A targeting vector containing a PGK-neomycin cassette, in reverse orientation, was used to disrupt an exon that corresponds to human exon 11 resulting in the deletion of 68 base pairs. The construct was electroporated into 129P2/OlaHsd derived E14K embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were bred to C57BL/6J to achieve germline transmission. The mice were then backcrossed to C57BL/6 for at least 9 generations. Upon arrival, sperm was cryopreserved. To establish a live colony, an aliquot of frozen sperm is used to fertilize C57BL/6J.

Allele

Symbol: Msh2^tm1Mak
Name: targeted mutation 1, Tak W Mak
MGI accession ID: MGI:1857940
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Msh2
Marker name: mutS homolog 2
Chromosome: 17
Strain of origin: 129P2/OlaHsd
Molecular note: A neomycin resistance cassette was inserted in an antisense orientation in an exon of the gene that corresponded to exon 11 of the human gene, resulting in the deletion of 68 bp (1959 - 2026). Western blots of protein extracts from tail fibroblasts of homozygous mutant mice showed no detectable protein expressed for the targeted gene.