Mouse model with humanized liver enables preclinical studies

摘要

In 2001, Norman Kneteman, David Mercer and Lome Tyrrell published a report on a SCID-Alb-uPA mouse model with a humanized liver1 and founded KMT Hepatech to support the model's application for the study of a range of liver-based diseases. The University of Alberta spin-out provides preclinical development research services to pharmaceutical and biotech companies. The KMT Mouse has a severe combined immunodeficiency (SCID) mutation that prevents the rejection of transplanted foreign hepatocytes. The uPAtransgene causes overproduction of the uPA protein in mouse hepatocytes, which results in hepatocyte death and subacute liver failure and provides a stimulus for hepatocyte proliferation. Transplanted human liver cells rapidly expand and replace the mouse liver cells, resulting in a highly humanized liver within the mouse. The resulting livers contain up to 95% viable, proliferating and differentiating human liver cells. The humanized liver develops complex architectural features and expresses human proteins in appropriate amounts, providing an in vivo approach for the investigation of human liver function and disease (Fig.l).