Mice hemizygous for the Msx2-CreERT transgene are viable and fertile, with expression of a tamoxifen-inducible Cre recombinase (Cre-ERT) directed to apical ectodermal ridge (AER) of the developing limb by the -0.5 kb promoter region from the mouse homeobox msh-like 2 locus (Msx2). CreERT fusion gene activity is inducible; observed following tamoxifen administration. When Msx2-CreERT transgenic mice are bred with mice containing loxP-flanked sequences, tamoxifen-inducible Cre-mediated recombination will result in deletion of the floxed sequences in the Msx2-expressing cells of the offspring (AER of the developing limb). The donating investigator has not determined the phenotype of homozygous mice to date (May 2012).
The Cre-ERT fusion protein consists of Cre recombinase fused to a G521R mutant form of the human estrogen receptor binding domain 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, Cre-ERT 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.
