Induction of gene mutations in mice: the multiple endpoint approach.
The multiple endpoint mammalian mutagenesis approach developed in our institute screens in the same animal for recessive specific locus alleles at 7 loci, approximately 30 loci coding for dominant cataract mutations, 23 loci controlling protein-charge changes and 12 loci for enzyme-activity alterations. Experiments to screen for the approximately 70 loci in the same offspring of treated male mice were performed with ethylnitrosourea (ENU), procarbazine and X-rays. Mutations were recovered for each genetic endpoint in all treatment groups where a sufficient number of offspring was scored. The observed per locus mutation rate for the different genetic endpoints after spermatogonial treatment with 250 mg/kg ENU was 93.6 X 10(-5) for specific locus mutations, 66.0 X 10(-5) for enzyme-activity mutations, 6.1 X 10(-5) for dominant cataract mutations, and 3.1 X 10(-5) for protein-charge mutations. In all experiments the mutation rates to specific locus and enzyme-activity alleles were higher than the mutation rates to either dominant cataract or protein-charge alleles. The mutations were confirmed by breeding tests.
D000818:Animals; D002386:Cataract / Q000235:genetics; D005799:Genes, Dominant; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009152:Mutagenicity Tests; D009154:Mutation; D010641:Phenotype; D012107:Research Design