Journal
TOXICOLOGIC PATHOLOGY
Volume 36, Issue 4, Pages 581-591Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/0192623308318212
Keywords
chimeric mouse; humanized liver; human hepatocyte; bile canaliculi; cytochrome P450; multidrug resistance protein; acetaminophen
Categories
Ask authors/readers for more resources
A human hepatocyte-transplanted chimeric mouse has been established by transplantation of human hepatocytes to urokinase-type plasminogen activator transgenic/severe combined immunodeficiency (uPA(+/+)/SCID) mice. These chimeric mice have various amounts of human hepatocytes that proliferate extensively and progressively replace mouse hepatocytes. In the chimeric liver, hepatic cords and sinusoid-like structures were observed. The human hepatocytes expressed human albumin, human cytochrome P450 enzymes, and human transporter proteins. Furthermore, electron microscopic analysis demonstrated bile canaliculi associated with human hepatocytes in the chimeric mouse livers. These results indicate that the chimeric mouse livers contain functionally intact and differentiated human hepatocytes. Additionally, the toxicologic response of hepatocytes to acetaminophen ( APAP) administration was compared in normal and chimeric mouse livers. Following 1,400 mg/kg APAP, mild hepatocellular degeneration was observed in the human hepatocyte areas in the chimeric mice, compared with severe centrilobular hepatocellular necrosis in the ICR mouse livers. In conclusion, these chimeric livers contain functionally differentiated human hepatocytes, and are less susceptible to APAP toxicity, compared to ICR mice.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available