One can use recombinant DNA techniques to make a “knockout” mutation in the gene in an embryonic stem (ES) cell line (one selects for replacement, by homologous recombination, of a wild type copy of the gene by an engineered mutant form of the gene). This mutated cell can then be introduced into a blastocyst; from this, chimeric mice, and after appropriate crosses, germ cells carrying the mutated gene can be obtained.