Exon 2 was replaced with a cDNA containing human ABCC2 exons 2-32 and a polyA signal and a neo cassette was inserted via homologous recombination. Flp mediated recombination removed the neo cassette. Quantitative PCR analysis confirmed absence of expression of the mouse gene and stable expression of the human gene in the liver kidney and intestines of homozygous mice. Expression levels of the human gene are elevated compared to expression levels of the mouse gene. Western blot analysis confirmed the expression of the human protein and absence of the mouse protein in the liver, kidney and intestines from homozygous mice.