3110082I17Rik-KO Mouse

3110082I17Rik, an ortholog of human C7orf50, encodes a hormone named Cholesin. Cholesin is involved in the regulation of cholesterol metabolism, playing a crucial role in maintaining cholesterol homeostasis through its associated pathway of inhibiting PKA signaling to suppress SREBP2-controlled cholesterol synthesis. Genetic models, like mouse models, are valuable for studying its function [1].

In mice, 3110082I17Rik-encoded Cholesin is secreted from the intestine in response to cholesterol absorption. It binds to GPR146, an orphan G-protein-coupled receptor. Through this interaction, it inhibits PKA signaling, which in turn suppresses SREBP2-controlled cholesterol synthesis in the liver, reducing circulating cholesterol levels. This reveals that the Cholesin-GPR146 axis mediates the inhibitory effect of intestinal cholesterol absorption on hepatic cholesterol synthesis [1].

In conclusion, 3110082I17Rik, via encoding Cholesin, is essential for regulating cholesterol metabolism. The study of 3110082I17Rik in mouse models contributes to understanding its role in maintaining cholesterol homeostasis, holding promise for combating hypercholesterolemia and atherosclerosis [1].

References:

1. Hu, Xiaoli, Chen, Fengyi, Jia, Liangjie, Zhang, Huijie, Wang, Yiguo. 2024. A gut-derived hormone regulates cholesterol metabolism. In Cell, 187, 1685-1700.e18. doi:10.1016/j.cell.2024.02.024. https://pubmed.ncbi.nlm.nih.gov/38503280/