Chemical Mutagenesis in Mice

Mutants have been the most important tool to obtain insight into the biological function of genes. In the post genome era, the mouse plays a major role as a model system for functional genome analysis and the molecular understanding of human diseases. This requires a large number of mutants similar to the collections available from other model organisms such as D. melanogaster and C. elegans. To fully apply the power of genetics multiple alleles of the same gene such as hypomorphs or hypermorphs are required. Efficient production of mouse mutants showing specific phenotypes can be achieved by using chemical or physical mutagens. Ethylnitroso-Urea (ENU) is the most powerful chemical mutagen known. The application of ENU-mutagenesis and other physical and chemical mutagens is reviewed and discussed in this chapter in the context of a new era of functional genomics. Strategies for mapping and cloning the mutations are also described in the chapter. Alteration of the genotype by chemical mutagenesis might alter the phenotype. In order to find those alterations comprehensive phenotyping protocols are applied. The chapter presents an overview of commonly used phenotyping protocols in a wide range of medically relevant areas. In addition, a short review is also given on chemical mutagenesis of embryonic stem cells.