Spontaneous mutation during fetal development and post-natal growth

被引:28
作者
Paashuis-Lew, YRM [1 ]
Heddle, JA [1 ]
机构
[1] York Univ, N York, ON M3J 1P3, Canada
基金
加拿大自然科学与工程研究理事会;
关键词
D O I
10.1093/mutage/13.6.613
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Somatic mutations seem to accumulate slowly with age during adult life in both mice and men. There is, however, a substantial mutant frequency at birth, suggesting that the rate of accumulation is much higher before birth. This suggests that DNA replication plays an important role in the generation of spontaneous mutations. Since most cell division and accompanying DNA replication occurs early in development, more mutations would arise during growth and development. Indeed, if the mutations are genetically neutral, the mutant frequency would rise very rapidly during early fetal growth, more slowly during later fetal growth and development and still more slowly after birth. To test this hypothesis, we have assayed the mutant frequencies from before birth to 28 days after birth, by which time most growth has occurred. We have used the F-1 mice generated by crossing SWR females and Muta(TM)Mouse males. The Muta(TM)Mouse has a rescuable lacZ/lambda shuttle vector that can be assayed for an in vivo mutation in an in vitro system. Up to and including birth we assayed the entire animal for mutants; at 14 and 28 days after birth we assayed the small intestine. The data show that, as expected, many mutations arise early in development, by 12.5 days after conception, and confirms the non-linearity of mutation with age. In these mice, about one third of mutations arise before birth, about one third during growth to adulthood and the remaining during the rest of the animal's life, although this depends somewhat on the tissue.
引用
收藏
页码:613 / 617
页数:5
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