Foxp3^{EGFP-cre-ERT2} mutant mice contain an internal ribosome entry site (IRES) and an enhanced green fluorescent protein (EGFP) fused to a CreER^T2 fusion gene (Cre recombinase fused to a G400V/M543A/L544A triple mutation of the human estrogen receptor ligand binding domain) downstream of the internal stop codon of the forkhead box P3 (Foxp3) gene. Homozygous females and hemizygous males are viable, fertile, and normal in size. FOXP3 is a transcription factor required for the development and function of regulatory T (T _reg) cells, which are required for suppression of self-reactive T cells and prevention of some autoimmune diseases. In these mice, EGFP expression is evident in FOXP3⁺ T_reg cells. Cre-ER^T2 fusion gene activity is inducible; observed in the same cells only following tamoxifen administration. When Foxp3^{EGFP-cre-ERT2} mice are bred with mice containing loxP-flanked sequence, tamoxifen-inducible, Cre-mediated recombination will result in deletion of the floxed sequences in T _reg cells of the offspring. For example, when these mice are bred with mice containing the Gt(ROSA)26Sortm1(EYFP)Cos allele, deletion of the floxed-STOP cassette in T _reg cells results in 3 populations of CD4⁺ cells: unlabeled FOXP3^- cells, EGFP⁺ YFP^- FOXP3⁺ cells, and EGFP⁺ YFP⁺ FOXP3⁺ cells. These mice may be useful for studying lineage stability and genetic mapping of regulatory T cells.

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.