Grompe Markus
Oregon Stem Cell Center, Department of Pediatrics, Oregon Health and Science University, Portland, OR, 97239-3098, USA.
Adv Exp Med Biol. 2017;959:215-230. doi: 10.1007/978-3-319-55780-9_20.
Several animal models of Fah deficiency have been developed, including mice, pigs and most recently rats. Initially, the murine models were developed with the intent to mirror the human disease for pathophysiologic and therapeutic studies. However, it soon became apparent that Fah-positive hepatocytes have a potent selective growth advantage in mutant liver and can extensively repopulate the diseased organ. For this reason, Fah mutant mice have become a workhorse for liver biology and are widely used in liver stem cell and hepatic gene therapy research. Immune deficient Fah-knockout mice can be repopulated with human hepatocytes, creating "mice with human livers". These chimeric animals have become an important preclinical model for infectious diseases, metabolism and gene therapy. The potent expansion of human hepatocytes in Fah knockout mice has given rise to the concept of using Fah mutants as living bioreactors to produce large quantities of fully mature hepatocytes. As a consequence, larger animal models of Fah deficiency have recently been developed.
已经开发出几种法氏缺陷（Fah deficiency）的动物模型，包括小鼠、猪，最近还有大鼠。最初，开发小鼠模型的目的是为了在病理生理学和治疗研究中模拟人类疾病。然而，很快就发现，Fah阳性肝细胞在突变肝脏中具有强大的选择性生长优势，并且可以广泛地重新填充患病器官。因此，Fah突变小鼠已成为肝脏生物学研究的主力，广泛应用于肝干细胞和肝脏基因治疗研究。免疫缺陷的Fah基因敲除小鼠可以用人肝细胞重新填充，从而创建“人肝小鼠”。这些嵌合动物已成为传染病、代谢和基因治疗的重要临床前模型。Fah基因敲除小鼠中人类肝细胞的强大扩增引发了将Fah突变体用作活体生物反应器以大量生产完全成熟肝细胞的概念。因此，最近已开发出更大的Fah缺陷动物模型。
