While mice heterozygous for this En1-CreERT1 mutation are viable and fertile, homozygotes die at birth. Because the Cre-ERT1 fusion gene is inserted between the transcriptional start site and the first exon of the engrailed 1 (En1) gene, tamoxifen-inducible cre activity is controlled by the endogenous En1 regulatory elements. The Cre-ERT1 fusion protein consists of 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) and, with lesser sensitivity, ICI 182780. Restricted to the cytoplasm, Cre-ERT1 can only gain access to the nuclear compartment after exposure to OHT. To counteract the mixed estrogen agonist effects of tamoxifen injections, which can result in late fetal abortions in pregnant mice, progesterone may be coadministered. When these En1-CreERT1 mice are bred with mice containing a loxP-flanked sequence of interest, tamoxifen-inducible, Cre-mediated recombination will result in deletion of the flanked sequences in En1-expressing tissues (including the mesencephalon and rhombomere 1, as well as the developing cerebellum, dermis, and limbs).
Of note, these mice may also be useful in conjunction with other engrailed mutants (such as Stock No. 007912, Stock No. 007916, Stock No. 007918, Stock No. 007924, and Stock No. 007925).
