The human genome has been almost completely sequenced, and at least 30,000 genes have been found (1 ). Systematic studies of gene expression patterns by using cDNA microarrays have provided a powerful approach to molecular dissection of cells and tissues by comparing expression levels of tens of thousands of these genes at a time. Even insight into signaling pathways has been gained (2 ,3 ). However, information about the in vivo function of the various genes, especially disease genes, still requires the development of animal models carrying particular mutations. Several mouse mutagenesis projects (see Chapter 13 ) have been started during the last decade, and the number of mutant mice generated by targeted mutagenesis in mouse embryonic stem (ES) cells has increased exponentially (4 –7 ).