Somatic cells as indicators of germinal mutations in the mouse

In attempts to find a prescreen for mutagens that may induce heritable mutations in mammals, an in vivo somatic mutation test has been developed in the mouse that uses a localized gene product (hair pigment), is relatively fast and cheap, and gives results that have some predictive value for point mutation induction in spermatogonia. Embryos heterozygous at specific coat color loci are exposed to the presumptive mutagen, and 3 weeks later the fur is observed for spots of altered color. It is possible to distinguish spots resulting from expression of the recessive (RS's) from spots having various other causes. In tests with seven compounds, mutation rates per locus and unit dose have been calculated on the assumption that 175 cells are at risk per 10¼-day embryo (a number derived from distribution of spot proportions). These rates are found to be roughly parallel to, but uniformly higher than spermatogonial point-mutation rates for the same seven compounds. The higher somatic rates are presumably due to the fact that RS's can result from several genetic mechanisms besides point mutations. The spot test, which has not to date given any false negatives, may thus be considered a useful in vivo prescreen for heritable germinal mutations in mammals.