Mutation frequency declines during spermatogenesis in young mice but increases in old mice

AUTOR(ES)

Walter, Christi A.

FONTE

The National Academy of Sciences

RESUMO

Five percent of live-born human offspring will have a genetic disorder. Of these, 20% are because of germ-line de novo mutations. Several genetic diseases, such as neurofibromatosis and Duchenne muscular dystrophy, are associated with a high percentage of de novo germ-line mutations. Until recently, a direct analysis of spontaneous mutation frequencies in mammalian germ cells has been prevented by technical limitations. We have measured spontaneous mutation frequencies in a lacI transgene by using enriched populations of specific spermatogenic cell types. Similar to previously published results, we observed a lower mutation frequency for seminiferous tubule cell preparations, which contain all stages of spermatogenesis, relative to somatic tissues. We made the unexpected observation of a decline in mutation frequency during spermatogenesis, such that the mutation frequencies of type B spermatogonia and all subsequent stages of spermatogenesis are lower than the frequency for primitive type A spermatogonia. In addition, spermatogenic cells from old mice have significantly increased mutation frequencies compared with spermatogenic cells from young or middle-aged mice. Finally, the mutation frequency was observed to increase during spermiogenesis in postreplicative cell types when spermatogenic cells were obtained from old mice.

Documentos Relacionados

• Chloroplast-Targeted ERD1 Protein Declines but Its mRNA Increases during Senescence in Arabidopsis1
• Methylation of unique sequence DNA during spermatogenesis in mice.
• Neuromuscular transmission and correlative morphology in young and old mice
• Symplastic spermatids (sys): a recessive insertional mutation in mice causing a defect in spermatogenesis.
• Patterns of Spontaneous and Radiation Induced Mutation Rates during Spermatogenesis in Drosophila Melanogaster