Transgenic mouse for targeted recombination mediated by modified Cre-ER

A method for producing spatio-temporally-controlled site-specific somatic recombinations in a mouse, wherein one or more gene or intergenic DNA sequences of interest naturally belonging to the genome of said mouse have been recombined, comprising:

• a) obtaining a transgenic mouse, wherein said transgenic mouse comprises a transgene encoding:
• (i) a Cre fusion protein comprising sequentially:
• (1) a Cre recombinase protein;
• a hinge region of at least 15 amino acids;
• a polypeptide comprising the ligand binding domain of the human nuclear estrogen receptor, or of a vertebrate nuclear estrogen receptor, said polypeptide exhibiting at least one mutation relative to the wild-type form of said ligand binding domains;
• and
• (2) said Cre fusion protein has a negligible, or even zero recombinase activity in the absence of a synthetic ligand endowed with antiestrogenic activity, the recombinase activity being induced by low dose of the synthetic ligand;
• (ii) one or more gene or intergenic DNA sequences of interest, naturally belonging to the mouse genome, flanked by one or more recognition sites for a Cre recombinase protein,
• b) administering to said transgenic mouse a low dose of said synthetic ligand in order to induce Cre-mediated recombination;
• and
• c) said gene or intergenic DNA sequences of interest undergo a site specific somatic recombination, as a result of the induction by said synthetic ligand, in at least 90% of the targeted cells of said mouse, whereas said gene or intergenic sequences of interest underwent recombination in less than 5% of the targeted cells of said mouse before step b).