Characterization of dominant cataract mutations in mice: penetrance, fertility and homozygous viability of mutations recovered after 250 mg/kg ethylnitrosourea paternal treatment

Abstract

SUMMARYSeventeen dominant cataract mutations of the mouse recovered in ethylnitrosourea mutagenesis experiments have been genetically characterized as to penetrance, fertility, and homozygous viability. Nine mutations were shown to be fully penetrant with no fertility effects, four mutations were classified as having reduced penetrance with no fertility effects, one mutation had reduced penetrance and reduced fertility, two mutations were shown to have a reduced frequency of mutant offspring due to penetrance and viability effects, and one mutation most likely has a reduced viability of carrier individuals. Of the eleven mutations for which definitive homozygous viability data were obtained, ten were shown to be homozygous viable and only one was shown to be homozygous lethal. In similar experiments in which dominant cataract, dominant skeletal or dominant visible mutations were recovered after radiation treatment, comparable frequencies of mutations with reduced penetrance were observed but there was a strikingly higher frequency of homozygous lethal mutations. These observations support the hypothesis of a qualitative difference in the mutations recovered after ethylnitrosourea as compared to radiation treatment. Finally, it is argued that a systematic comparison of the induced mutation rates to dominant and recessive alleles with subsequent genetic characterization of the recovered mutations provides a critical set of data necessary for an improvement in the indirect and direct procedures of genetic risk estimation.