Methods to improve the production of transgenic animals are being deve
loped. Conventional transgenesis, involving microinjection of DNA into
fertilized eggs, has a number of limitations. These result from the i
nability to control both the site of transgene insertion and the numbe
r of gene copies inserted. The approach described seeks to overcome th
ese problems and to allow single copy insertion of transgenes into a d
efined site in animal genomes. The method involves the use of embryoni
c stem cells, gene targeting and the FLP recombinase system.