KMT Mouse Model
KMT MouseTM is the trade name for proprietary chimeric mouse with humanized liver with up to 95% of replacement, first reported in 2001 by KMT Hepatech founders (uPA/SCID mice transplanted with human hepatocytes).
Immunodeficient mice (homozygous for both the scid trait and Alb/uPA transgene) are transplanted via splenic injection with isolated human hepatocytes taken from noninfected human donors. The transplanted cells translocate to and engraft within the mouse's liver.
Human hepatocytes repopulate the mouse liver in an organized fashion and retain long term normal pharmacological responses. Human hepatocytes in the mouse liver are functional and secrete a variety of hepatic proteins. The replacement of mouse hepatocytes with human hepatocytes generally correlates with human albumin (hAlb) levels.
Upon engraftment, the KMT MouseTM with humanized liver can be inoculated with human serum containing infectious viral particles (HCV, HBV) and they support durable replication of the virus at levels observed in humans. The model provides an authentic viral infection utilizing human liver cells infected with virus (or malaria parasite) in a true in vivo settings.
The non-infected KMT MouseTM can be utilized to address early evaluation of toxicity in human hepatocytes and characterization of human-type drug and lipoprotein metabolism. These applications are beneficial for safety assessment and DMPK studies.
Chimeric Mouse Features
- Up to 95% of human hepatocyte engraftment
Human hepatocytes in the mouse liver are functional and secrete a variety of hepatic proteins like albumin, alpha-1 antitrypsin, apolipoprotein A, apolipoprotein B, apolipoprotein E and several clotting factors and complement proteins
- Human phase I metabolizing enzymes
- Human phase II metabolizing enzymes
- Human transporters
- Hepatic cords
- Sinusoid-like structures
- Bile canaliculi associated with human hepatocytes