title: Induction and manifestation of hereditary cataracts.
abstract: A cataract is an opacity of the lens causing a reduction of visual function. The organogenesis of the lens in various mammals is similar. Therefore, a cataract mutation in mice can be directly compared with cataracts in man. Screening for dominant cataracts in mice was combined with the scoring of specific locus mutations. This combination increases the number of scorable loci, allows the comparison of unselected and selected loci and makes possible a systematic comparison of dominant and recessive mutations. In a combined experiment, dominant cataract and specific locus mutations were scored in the same offspring of mice after treatment of spermatogonia. In radiation experiments the induced frequency of dominant cataracts in spermatogonia was after single exposure 4.5 - 5.5 X 10(-5) mutations/gamete/Gy and for specific locus mutations 1.6 - 2.8 X 10(-5) mutations/locus/Gy. In experiments with ethylnitrosourea (ENU) the induced frequency of dominant cataracts was 0.7 - 1.3 X 10(-5) (mutations/gamete)/(mg ENU/kg body weight) and for specific locus mutations 2.6 - 3.3 X 10(-6) (mutations/locus)/(mg ENU/kg body weight). The radiation-induced mutation rate can be used for the direct estimation of the genetic risk in humans. The genetically significant population dose for 19 000 offspring in Hiroshima and Nagasaki was estimated to be 1.1 X 10(6) man-rem, absorbed at high dose rate. For the 19 000 offspring one would expect less than 1 radiation-induced dominant cataract and a total of 20 - 25 dominant mutations. If the number of dominant and recessive loci are equal one would expect in addition the induction of 250 recessive mutations in this population. Chemically induced dominant cataract mutations could be used to determine the allowable level of exposure for a single compound. The genetically characterized mutations will be an ideal source for studies in the field of developmental genetics. The investigation of alpha-, beta-, and gamma-crystallins by electrophoretic methods, the activity determinations of enzymes and the systematic use of cDNA hybridization may lead to an understanding of the genesis of dominant cataracts in mice and man.
mesh_terms: D000818:Animals; D002386:Cataract / Q000235:genetics* / Q000473:pathology; D002874:Chromosome Mapping; D004195:Disease Models, Animal; D005260:Female; D005799:Genes, Dominant; D005808:Genes, Recessive; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009154:Mutation; D010641:Phenotype; D012306:Risk