Fh1-flox Mouse

Fh1, or fumarate hydratase 1, is a gene with diverse functions. In the context of mammalian biology, it has been associated with the control of Atf4 expression [4]. In plants, the Arabidopsis thaliana FH1 (At3g25500) is a Class I membrane-anchored formin that contributes to actin dynamics, microtubule stability, and is involved in cell morphogenesis and organ development [2,3,5].

In a mouse model of non-alcoholic steatohepatitis (NASH), the Klf10-Fh1 axis was found to be crucial. Hepatocyte-specific knockout of Klf10 (Klf10LKO) increased lipid accumulation, cell death, inflammation, and fibrosis in NASH-diet-fed mice and reduced the protective effects of treadmill exercise against NASH. Klf10 promotes the expression of Fh1, which in turn reduces fumarate accumulation in hepatocytes. This decreases the trimethyl (me3) levels of histone 3 lysine 4 (H3K4me3) on lipogenic genes promoters to attenuate lipogenesis, thus ameliorating NASH-related symptoms [1].

In summary, Fh1 plays important roles in both mammalian and plant biological processes. In mice, the Fh1-related Klf10-Fh1 axis is significant in the context of NASH, where its manipulation through gene knockout models has revealed its role in regulating lipid metabolism, inflammation, and fibrosis, providing insights into potential therapeutic strategies for NASH.