The targeting vector is designed to insert an internal ribosome entry site (IRES) fused to flpo recombinase gene (a codon-optimized flpe gene modified for translation in mammalian cells and higher recombination efficiency in cells and in mice), followed by a loxP-flanked neo cassette, downstream of the stop codon of the gene. Cre-mediated recombination removed the floxed neo cassette.