Fah-flox Mouse

Fah, short for fumarylacetoacetate hydrolase, is the last enzyme in the tyrosine catabolic pathway. It belongs to the FAH superfamily of enzymes, whose members share conserved regions forming the FAH-domain and catalyze various reactions. In both prokaryotes and eukaryotes, these enzymes are essential for degrading aromatic compounds. In prokaryotes, they help generate energy and useful metabolites from complex carbon sources, while in eukaryotes, they may have acquired regulatory functions beyond catabolism [2].

Several animal models of Fah deficiency have been developed, such as mice, pigs, and rats. Fah-positive hepatocytes have a selective growth advantage in mutant livers, enabling extensive repopulation of the diseased organ. Thus, Fah-knockout mice have become crucial for liver biology research, including studies on liver stem cells and hepatic gene therapy. Immune-deficient Fah-knockout mice can be repopulated with human hepatocytes, creating “mice with human livers” which serve as important preclinical models for infectious diseases, metabolism, and gene therapy. Additionally, Fah-knockout mouse models have also been used to study BEC-to-hepatocyte conversion and sleep-wake pattern alterations related to chronic tyrosinemia [1,3,4].

In conclusion, Fah is essential for tyrosine catabolism and has implications in multiple biological processes. Fah-knockout mouse models have significantly contributed to research in liver-related diseases, infectious diseases, metabolism, and the understanding of BEC-to-hepatocyte conversion and sleep-wake pattern regulation. These models provide valuable insights into the role of Fah in health and disease, facilitating further exploration of potential therapeutic strategies.