This strain expresses a fusion product involving Cre recombinase and a mutant form of the human estrogen receptor ligand binding domain (Cre/ERT2) from the endogenous Shh locus. The mutant human estrogen receptor does not bind natural ligand at physiological concentrations but will bind the synthetic ligand, 4-hydroxytamoxifen. Restricted to the cytoplasm, the Cre/ESR1 protein can only gain access to the nuclear compartment after exposure to tamoxifen. Tamoxifen administration induces Cre recombinase expression in all cells of the mouse limb that express the endogenous gene resulting in the deletion of the first 35 base pairs following the ATG. Introduction of tamoxifen at E10.5 resulted in the labeling of LacZ-positive cells that contributed to digit 5 and the posterior half of digit 4 in E14.5 limbs. Injection of tamoxifen at E11.5 resulted in the labeling of cells only in digit 5. Homozygous mice are not viable or fertile. Heterozygous mutant mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. This mutant mouse strain may be useful in studies of limb patterning and development.

Tamoxifen administration in these mice induces Cre recombinase expression in all cells of the mouse limb that express the endogenous gene. Cells that contribute to more anterior digits cease to express Shh at an earlier stage of limb development.This mutant mouse strain may be useful in studies of limb patterning and development.