The effects of MSH2 deficiency on spontaneous and radiation-induced mutation rates in the mouse germline |
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Authors: | Burr Karen L-A van Duyn-Goedhart Annemarie Hickenbotham Peter Monger Karen van Buul Paul P W Dubrova Yuri E |
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Institution: | Department of Genetics, University of Leicester, University Road, Leicester LE1 7RH, United Kingdom. |
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Abstract: | 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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