Functional genomics the old-fashioned way: chemical mutagenesis in mice

Genetic studies using mutants have led to a greater understanding of the mechanisms underlying the physiology, biochemistry and development of organisms. The increasing availability of complete genome sequences has stimulated genome-wide mutagenesis approaches in model organisms. In an ideal model system, it would be possible to choose from a series of mutations in any given gene to study its function, regulation and interaction with other genes; flies and worms with their rich mutant resources provide such models. Because the mouse is a powerful vertebrate model for human disease, it would be advantageous to have an equally comprehensive mutant collection. Recently, much to the joy of the mouse community, two papers, describe screens to generate such a collection. In an ongoing screen, the groups of Brown and Balling have generated over 40,000 F1 mutant mice by treating males with the super mutagen N-ethyl-N-nitrosourea. 300-500 mice are being screened each week using various objective tests and paradigms for morphological, developmental, clinical and behavioral abnormalities. In combination, these analyses have produced an unbiased set of about 700 new dominant, semidominant and recessive mutations.