PMID:16728433

Citation	Hegan, DC, Narayanan, L, Jirik, FR, Edelmann, W, Liskay, RM and Glazer, PM (2006) Differing patterns of genetic instability in mice deficient in the mismatch repair genes Pms2, Mlh1, Msh2, Msh3 and Msh6. Carcinogenesis 27:2402-8
Abstract	Defects in genes associated with DNA mismatch repair (MMR) have been linked to hereditary colon cancer. Because the MMR pathway includes multiple factors with both overlapping and divergent functions, we sought to compare the impact of deficiencies in each of several MMR genes on genetic instability using a collection of knock-out mouse models. We investigated mutation frequencies and patterns in MMR-deficient mice using two transgenic reporter genes, supFG1 and cII, in the context of mice deficient for Pms2, Mlh1, Msh2, Msh3 or Msh6 or both Msh2 and Msh3 or both Msh3 and Msh6. We found that the mean mutation frequencies of all of the MMR-deficient mice were significantly higher than the mean mutation frequencies of wild-type mice. Mlh1-deficient mice and Msh2-deficient mice had the highest mutation frequencies in a comparison of the single nullizygous mice. Of all the mice studied, mice nullizygous for both Msh2 and Msh3 and those nullizygous for both Msh3 and Msh6 displayed the greatest overall increases in mutation frequencies compared with wild-type mice. Sequence analysis of the mutated reporter genes revealed significant differences between the individual groups of MMR-deficient mice. Taken together, our results further characterize the functions of the MMR factors in mutation avoidance and provide in vivo correlation to biochemical models of the MMR pathway.
Links	PubMed PMC2612936 Online version:10.1093/carcin/bgl079
Keywords	Adaptor Proteins, Signal Transducing; Adenosine Triphosphatases/deficiency; Adenosine Triphosphatases/genetics; Animals; Carrier Proteins/genetics; Colonic Neoplasms/genetics; Crosses, Genetic; DNA Mismatch Repair; DNA Repair Enzymes/deficiency; DNA Repair Enzymes/genetics; DNA-Binding Proteins/deficiency; DNA-Binding Proteins/genetics; Genomic Instability; Humans; Mice; Mice, Knockout; Mice, Transgenic; MutS Homolog 2 Protein/deficiency; MutS Homolog 2 Protein/genetics; Mutation; Nuclear Proteins/deficiency; Nuclear Proteins/genetics; Proteins/genetics
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