Saturation mutagenesis for dominant eye morphological defects in the mouseMus musculus

We have summarized our extensive series of mutagenesis experiments to isola te dominant mutations in the mouse that express eye morphological defects. Thirty-two experimental groups in which parental mice were exposed to chemi cal mutagens or irradiation and a historical control group of the laborator y are presented. The largest series of experiments included parental exposu re to ethylnitrosourea or irradiation. A total of 203 dominant mutants were confirmed among 456,890 offspring screened, which represents one of the la rgest collections of mutations in the mouse affecting one organ following a systematic screen of offspring of mutagenized animals. The largest group o f mutations (92) was recovered in offspring of parental mice exposed to eth ylnitrosourea. The second largest group of mutations (62) was recovered in irradiation experiments. Fifty-six mutations recovered in ethylnitrosourea experiments have been mapped to 22 loci. The affected genes have been ident ified for a number of the recovered mutations including Cryga, Crygb, Cgyge , Pax6, Pax2, Mitf, Lim2, and Cx50. On the basis of our experiences, a numb er of considerations when undertaking such screens are discussed, including a) choice of mutagen, b) experimental design, and c) the criteria for such experiments to ensure that mutations at novel loci will be recovered.