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

The role of Msh2 in chromosome stability has been investigated in a targeted mouse model for HNPCC, Msh2 Delta 7N. 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 similar to 20% and similar to 45% wild-type levels respectively indicating a phenotypic effect of haploinsufficiency of the mouse Msh2 gene. (C) 2000 Cancer Research Campaign.