Germ cell mutations in mice

The most extensive set of information on the factors affecting mutation induction by chemical mutagens in mice has been obtained by use of the dominant lethal assay and the specific locus method. Dominant lethal mutations are caused by chromosomal aberrations, and they occur shortly before or after implantation. The specific locus method can be used to detect a variety of mutational events, ranging from intralocus changes to multilocus deletions. The scoring of recessive specific locus mutations can be combined with the detection of dominant cataract mutations in mice. With these methods, the following factors that influence the induced mutation rates have been identified: differential spermatogenic response, fractionation of doses (low-dose effects), different treatment conditions (combined treatment), different strains, different sexes, and differences in the response of recessive and dominant mutations. The importance of these factors for the evaluation of chemical mutagens has not generally been appreciated in genetic toxicology. However, they are important for the risk assessment of a chemical mutagen. In addition, the induction of specific locus mutations and of inherited dominant cataract mutations or dominant mutations affecting the skeleton of mice can be used to quantify human genetic risk due to a mutagen.