Mice hemizygous for the BAC Hsd17b1-icreERT2 transgene are viable, fertile, and normal in size with iCre-ERT2 expression directed by the hydroxysteroid (17-beta) dehydrogenase 1 (Hsd17b1) promoter/enhancer regions within the BAC transgene. These BAC mice express 8 copies of iCre-ERT2 protein in granulose cells of the ovarian follicles. iCre-ERT2 fusion gene activity is inducible and is observed only following tamoxifen administration. When these mice are bred with mice containing loxP-flanked sequence, tamoxifen-inducible, Cre-mediated recombination will result in deletion of the floxed sequences in the BAC-expressing cells of the offspring. These mice may be useful for studying gene function in ovarian granulose cells.
The iCre-ERT2 fusion protein consists of a codon-improved Cre recombinase fused to a triple mutant form of the human estrogen receptor which does not bind its natural ligand (17β-estradiol) at physiological concentrations but will bind the synthetic estrogen receptor ligands 4-hydroxytamoxifen (OHT or tamoxifen) and, with lesser sensitivity, ICI 182780. Restricted to the cytoplasm, iCre-ERT2 can only gain access to the nuclear compartment after exposure to tamoxifen. To counteract the mixed estrogen agonist effects of tamoxifen injections, which can result in late fetal abortions in pregnant mice, progesterone may be coadministered.
