Phenotypic characterization and genetic analysis of twenty dominant cataract mutations detected in offspring of irradiated male mice.

Abstract

SummaryTwenty autosomal dominant cataract mutations were detected among the offspring of male mice irradiated with γ- or X-rays. The single or fractionated doses ranged from 5.34 to 10.2 Gy. The phenotypic manifestation and penetrance of the mutations as well as fertility and viability of the mutants were studied by extensive breeding. Manifestation of 4 mutations was limited to the lens. Sixteen mutations were characterized by multiple ocular anomalies, of which 4 mutations also affected other organs of the body. Seventy per cent of the mutations caused severe opacity of the lens or lens and cornea. Homologous hereditary diseases in man would be juvenile cataracts with serious impairment of vision or blindness. Expressivity of the lens opacities was almost constant whereas the accompanied defects varied with respect to their severity in different individuals as well as in eyes of an individual. Phenotypic differences dependent on the genetic background could not be observed. Fourteen mutations were classified as mutations with complete penetrance without any effect on viability and fertility of heterozygotes. Four other mutations were shown to be fully penetrant but the viability of the heterozygotes was impaired. Two mutations had incomplete penetrance with no viability or fertility effects. Of the 14 mutations with complete penetrance and normal viability and fertility 6 were shown to be homozygous viable, 1 semi-lethal and 7 lethal.