Downstream of the translation termination codon of the endogenous gene was inserted an internal ribosomal entry site (IRES) followed by DNA encoding Cre recombinase joined to ERT2 and a frt site-flanked neomycin resistance cassette (IRES-CreERT2-FRT-neoR-FRT). ERT2 is a triply mutated (G400V, M543A, L544A) human estrogen receptor ligand-binding domain (LBD) that renders the fusion protein highly sensitive to activation by 4-hydroxytamoxifen, but unresponsive to the receptor's native ligands. (J:159445)