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.
Dr. Tak Mak, University Health Network / University of Toronto
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.
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 Name||targeted mutation 1, Tak W Mak|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Msh2, mutS homolog 2|
|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.|
While maintaining a live colony, these mice are bred as homozygotes.
When using the MSH2- mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #42057 in your Materials and Methods section.