Chimeric Rats for Liver Humanization

DESCRIPTION (provided by applicant): Yecuris has developed an in vivo genetic selection system (the FRG KO mouse) that permits extensive humanization of murine liver by transplantation with human hepatocytes. This model has many potential commercial applications in drug development and testing, both in the in vivo and in vitro markets, .The mouse, however, is a small rodent and therefore the number of human hepatocytes that can be obtained for in vitro studies is limited to 80-150 million hepatocytes/animal. A larger animal that could be similarly repopulated would provide significant cost savings and economy of scale. Furthermore, the rat is the animal model of choice in many preclinical applications, particularly toxicology. For these reasons, we decided to generate an FRG KO rat, with mutations completely analogous to those in the FRG KO mouse: Fumary lacetoacetate hydrolase (Fah), Rag2 and common gamma chain of the interleukin receptor (Il2rg). Using TALEN and other gene editing technologies, st