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The role of Msh2 in chromosome stability has been investigated in a targeted mouse model for HNPCC, Msh2Delta7N. Chromosome aberration frequencies were similar in bone marrow of Msh2(+/+), Msh2(+/-)and Msh2(-/-)mice and no differential effects of in vivo X-irradiation were noted. By contrast, the induction of sister-chromatid exchanges (SCEs) by methyl nitrosourea (MNU) was reduced in Msh2(-/-)and Msh2(+/-)cells to approximately 20% and approximately 45% wild-type levels respectively indicating a phenotypic effect of haploinsufficiency of the mouse Msh2 gene.

Evidence for Msh2 haploinsufficiency in mice revealed by MNU-induced sister-chromatid exchange analysis