Mouse models play an important role in the elucidation of molecular pathways underlying human disease. Mutations in mouse can be generated by a variety of techniques including those using inducing agents such ionizing radiation or chemicals and those that involve genetic manipulations such as transgenic insertions or knockouts. Random mutagenesis by ionizing radiation or chemical agents has a long tradition in classical genetics and has allowed the generation of a large number of mutant phenotypes. Ionizing radiation causes breaks in the chromosome, leading to deletions, translocations, and other gross chromosomal rearrangements. Chemical mutagens, which have been shown to produce a large number of mutations, are characterised by a differential spermatogenic response.