Knockout mice have become an excellent tool to cre-ate mouse models for genetic diseases and to elucidate the essential functions of important regulatory molecules (products from growth factor genes, on-cogenes, and developmental genes). Knockout mice are generated by gene targeting in embryonic stem (ES) cells. These mutated ES cells are injected into the recipient embryos to generate chimeric mice that contain tissues (including germ cells) derived from the mutated ES cells and pass the trait on to their offspring (see Figure 1 andrefs. 4 to 7).