MSH2 deficient mice are viable and susceptible to lymphoid tumours.
Alterations of the human MSH2 gene, a homologue of the bacterial MutS mismatch repair gene, co-segregate with the majority of hereditary non-polyposis colon cancer (HNPCC) cases. We have generated homozygous MSH2-/- mice. Surprisingly, these mice were found to be viable, produced offspring in a mendelian ratio and bred through at least two generations. Starting at two months of age homozygous-/- mice began, with high frequency, to develop lymphoid tumours that contained microsatellite instabilities. These data establish a direct link between MSH2 deficiency and the pathogenesis of cancer. These mutant mice should be good models to study the progression of tumours and also to screen carcinogenic and anti-cancer agents.
Reitmair
A H
AH
Amgen Institute, Department of Medical Biophysics, University of Toronto, Canada.
Schmits
R
R
Ewel
A
A
Bapat
B
B
Redston
M
M
Mitri
A
A
Waterhouse
P
P
Mittrücker
H W
HW
Wakeham
A
A
Liu
B
B
D000818:Animals; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis* / Q000235:genetics; D004276:DNA, Satellite / Q000032:analysis*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005656:Fungal Proteins; D018390:Gene Targeting; D005838:Genotype; D006801:Humans; D008221:Lymphoid Tissue / Q000473:pathology; D008297:Male; D008540:Meiosis; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D051718:MutS Homolog 2 Protein; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology; D013045:Species Specificity
D004273:DNA, Neoplasm; D004276:DNA, Satellite; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D051718:MutS Homolog 2 Protein