Hepatic gene expression in various different lots of chimeric mice with highly humanized liver

In addition to immunodeficiency, host mice for chimeric mice with highly humanized liver should have hepatic malfunction in order to allow higher replacement rate of human hepatocytes in the liver. Urokinase-type plasminogen activator (uPA) whole gene transfer is often employed to achieve hepatic malfunction in the host mice. We have established uPA cDNA transfer that is far stable, as compared with traditional whole uPA gene transfer. Hepatic gene expression was quite similar between whole uPA gene transfer and uPA cDNA transfer after transplantation of the same lot of human hepatocyte (BD195),, as compared with the variation of gene expression after transplantation of different lots of human hepatocytes to host mice with whole uPA gene transfer. In SCID host mice with whole uPA gene transfer, 4 different lots of human hepatocytes were transplanted. One lot of human hepatocyte (BD195) was additionally transplanted to homozygous uPA cDNA transfer- and heterozygous uPA cDNA transfer-derived host mice.