The entire ORF of the Nkx2-2 gene including most of exon1, intron 1, and exon 2 is replaced by the codonimproved Cre-ORF and the polyA addition signal sequence (pA) followed by FRT-flanked neomycin selection cassette (PGK-neo) by homologous recomibination in ES cells. (J:222414)