The effects of MSH2 deficiency on spontaneous and radiation-induced mutation rates in the mouse germline

Mutation rates at two expanded simple tandem repeat (ESTR) loci were studied in the germline of mismatch repair deficient Msh2 knock-out mice. Spontaneous mutation rates in homozygous Msh2−/− males were significantly higher than those in isogenic wild-type (Msh2+/+) and heterozygous (Msh2+/−) mice. In contrast, the irradiated Msh2−/− mice did not show any detectable increases in their mutation rate, whereas significant ESTR mutation induction was observed in the irradiated Msh2+/+ and Msh2+/− animals. Considering these data and the results of other publications, we propose that the Msh2-deficient mice possess a mutator phenotype in their germline and somatic tissues while the loss of a single Msh2 allele does not affect the stability of heterozygotes.