Heterozygous mice are viable and fertile, normal in size and do not display any gross physical or behavioral abnormalities. The DI states that the strain is homozygous lethal. The Foxd1GCE allele expresses an eGFPCreERT2 fusion protein (EGFP and creERT2 fusion protein) from the Foxd1 promoter/enhancer elements. Foxd1 is induced, and EGFP immunofluorescence is observed, during kidney development in metanephric mesenchyme in cells fated to become stromal cells of the kidney. Cre-ERT2 fusion gene activity is inducible; observed in the same cells only following tamoxifen administration. When Foxd1GCE mice are bred with mice containing loxP-flanked sequence, tamoxifen-inducible, Cre-mediated recombination will result in deletion of the floxed sequences in the FoxD1-expressing cells of the offspring. These mice may be useful for studying therapeutic strategies directly targeting pericyte differentiation in vivo and may productively impact fibrotic kidney disease.
The Cre-ERT2 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 or tamoxifen) and, with lesser sensitivity, ICI 182780. Restricted to the cytoplasm, Cre-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.
