The effects of MSH2 deficiency on spontaneous and radiation-induced mutation rates in the mouse germline.
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.
Burr
Karen L-A
KL
Department of Genetics, University of Leicester, University Road, Leicester LE1 7RH, United Kingdom.
van Duyn-Goedhart
Annemarie
A
Hickenbotham
Peter
P
Monger
Karen
K
van Buul
Paul P W
PP
Dubrova
Yuri E
YE
D000818:Animals; D005260:Female; D018095:Germ-Line Mutation / Q000528:radiation effects*; D006579:Heterozygote; D006720:Homozygote; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051718:MutS Homolog 2 Protein / Q000172:deficiency / Q000235:genetics*; D011836:Radiation Tolerance; D011839:Radiation, Ionizing; D020080:Tandem Repeat Sequences / Q000235:genetics*
C497173:Msh2 protein, mouse; D051718:MutS Homolog 2 Protein