Ligand-activated site-specific recombination in mice.
Current mouse gene targeting technology is unable to introduce somatic mutations at a chosen time and/or in a given tissue. We report here that conditional site-specific recombination can be achieved in mice using a new version of the Cre/lox system. The Cre recombinase has been fused to a mutated ligand-binding domain of the human estrogen receptor (ER) resulting in a tamoxifen-dependent Cre recombinase, Cre-ERT, which is activated by tamoxifen, but not by estradiol. Transgenic mice were generated expressing Cre-ERT under the control of a cytomegalovirus promoter. We show that excision of a chromosomally integrated gene flanked by loxP sites can be induced by administration of tamoxifen to these transgenic mice, whereas no excision could be detected in untreated animals. This conditional site-specific recombination system should allow the analysis of knockout phenotypes that cannot be addressed by conventional gene targeting.
Feil
R
R
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Université Louis Pasteur, Collège de France, C.U. de Strasbourg, France.
Brocard
J
J
Mascrez
B
B
LeMeur
M
M
Metzger
D
D
Chambon
P
P
D000818:Animals; D005786:Gene Expression Regulation; D005818:Genetic Engineering / Q000379:methods*; D019426:Integrases / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D051379:Mice; D008822:Mice, Transgenic; D011960:Receptors, Estrogen / Q000737:chemistry* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism*; D011995:Recombination, Genetic; D017384:Sequence Deletion; D013629:Tamoxifen / Q000494:pharmacology*; D019076:Transgenes / Q000235:genetics; D014764:Viral Proteins
D008024:Ligands; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; D013629:Tamoxifen; C045073:Cre recombinase; D019426:Integrases