A technique for deleting, mutating or otherwise inactivating a gene in a mouse. This laborious method involves transfecting a crippled gene into cultured embryonic stem cells, searching through the thousands of resulting clones for one in which the crippled gene exactly replaced the normal one (by homologous recombination), and inserting that cell back into a mouse blastocyst. The resulting mouse will be chimaeric but its germ cells will carry the deleted gene. A few rounds of careful breeding can then produce progeny in which both copies of the gene are inactivated.See Gene; Locus; Model Organisms.