Genetically modified mice for human hepatocyte xenotransplantation

摘要

One or more embodiments of the invention include an immunodeficient mouse that has been genetically modified to include a gene encoding a PiZ variant of human α-1 antitrypsin (AAT) (Glu342Lys), wherein the mouse comprises a human Mouse hepatocyte numbers are reduced compared to immunodeficient mice of the same type that express the PiZ variant of α-1 antitrypsin (Z-AAT) and do not express Z-AAT. An immunodeficient mouse that has been genetically modified to contain a gene encoding a PiZ variant of human AAT can be a genetically modified NSG, NRG or NOG mouse. The immunodeficient mouse can further include xenogeneic hepatocytes, such as human hepatocytes. Putative treatment of human liver disease can be evaluated in mice provided according to aspects of the present disclosure.