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, 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.
Bouffler
S D
SD
Radiation Effects Department, National Radiological Protection Board, Chilton, Didcot, Oxfordshire, OX11 0RQ, UK.
Hofland
N
N
Cox
R
R
Fodde
R
R
D000818:Animals; D020137:Base Pair Mismatch; D002869:Chromosome Aberrations; D002873:Chromosome Fragility; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000662:veterinary; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics* / Q000662:veterinary; D004260:DNA Repair; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D019656:Loss of Heterozygosity; D008770:Methylnitrosourea / Q000009:adverse effects; D051379:Mice; D051718:MutS Homolog 2 Protein; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D011839:Radiation, Ionizing; D012854:Sister Chromatid Exchange / Q000235:genetics*
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D008770:Methylnitrosourea; C497173:Msh2 protein, mouse; D051718:MutS Homolog 2 Protein