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

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    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
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