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-ray exposure. Mutations were recovered for each genetic endpoint in all treatment groups where a sufficient number of offspring was scored. ENU treatment is highly effective in inducing mutations to all genetic endpoints. The mutations were confirmed by breeding tests. The mutation rates to specific-locus and enzyme-activity alleles were both higher than the mutation rates to either dominant-cataract or protein-charge alleles. The advantages and possibilities of the multiple endpoint approach are discussed in detail.
D000818:Animals; D002386:Cataract / Q000209:etiology; D005038:Ethylnitrosourea / Q000633:toxicity; D005260:Female; D005799:Genes, Dominant; D007526:Isoelectric Point; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests; D009154:Mutation / Q000187:drug effects* / Q000528:radiation effects; D011344:Procarbazine / Q000633:toxicity; D011506:Proteins / Q000235:genetics; D012880:Skin Pigmentation; D013093:Spermatogonia / Q000187:drug effects / Q000528:radiation effects; D014965:X-Rays
D011506:Proteins; D011344:Procarbazine; D005038:Ethylnitrosourea