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 t hat conditional site-specific recombination can be achieved in mice us ing a new version of the Cre/lox system, The Cre recombinase has been fused to a mutated ligand-binding domain of the human estrogen recepto r (ER) resulting in a tamoxifen-dependent Cre recombinase, Cre-ER(T), which is activated by tamoxifen, but not by estradiol. Transgenic mice were generated expressing Cre-ER(T) under the control of a cytomegalo virus promoter. We show that excision of a chromosomally integrated ge ne flanked by loxP sites can be induced by administration of tamoxifen to these transgenic mice, whereas no excision could be detected in un treated animals. This conditional site-specific recombination system s hould allow the analysis of knockout phenotypes that cannot be address ed by conventional gene targeting.