Company claims mouse can provide pool of human hepatocytes for in vivo and in vitro DMPK and ADMET applications.
Yecuris introduced a humanized mouse model designed to allow researchers to grow and expand populations of human hepatocytes in vivo for research and drug testing. The FRG model has the genes Fah, Rag, and Ilrg knocked out.
Knocking out Fah yields mouse liver damage, the lack of Rag removes the part of the innate immune system that rejects other mouse cells, and knocking out Ilrg inactivates the part of the immune system that would prevent engraftment of cells from other species including humans, according to Yecuris.
The FRG mouse can either be repopulated with human donor cells of choice or repopulated from the company’s pool of prequalified donors. Animals can be provided with human hepatocytes that range from 5–95% of the total liver mass. Nonrepopulated FRG mice are also available for use as study controls. The firm claims the animals can live for more than a year in an appropriately controlled environment.
The availability of expanded hepatocytes not only provides for better supply consistency but means the same donor cells can be used in both in vivo and in vitro testing throughout the discovery process, Yecuris states.
“The FRG mouse model truly has exceeded our scientific expectations,” comments CSO, Markus Grompe, M.D. “After engraftment of human hepatocytes, the FRG knockout model exhibits a range of normal human liver functions including an abundance of human serum albumin, human lipids, enzymes, transporters, and bile acids. The hepatocytes cultured by this method are inducible, maintain mature phenotypes, and express human-like lipid and bile acid profiles.”
Yecuris was formed in 2007 to commercialize the FRG mouse technology, which was originally developed at Dr. Grompe’s laboratory at the Oregon Health and Sciences University. The mouse model was initially created to explore pathways for hereditary type I tyrosinemia. The company also offers human primary hepatocyte product lines for drug development, infectious diseases, and cancer biology.