Liver-specific Nr1h4 deletion in mice with human-like bile acid composition causes severe liver injury.

ABSTRACT: The farnesoid X receptor, encoded by NR1H4, is crucial for bile acid, lipid, and glucose metabolism. NR1H4 mutations in humans cause a severe liver injury called progressive familial intrahepatic cholestasis 5. However, Nr1h4 deletion in mice did not cause severe liver damage at a young age, likely because of the higher levels of hydrophilic bile acids synthesized by the mouse-specific bile acid metabolic enzymes Cyp2a12 and Cyp2c70. We aimed to assess hepatic NR1H4 function by taking advantage of the recently established Cyp2a12/Cyp2c70 double-knockout (CYPDKO) mouse model, which has a human-like bile acid composition containing mainly hydrophobic bile acids. Liver-specific Nr1h4-deficient CYPDKO mice were established using an adeno-associated virus-derived genome-editing method. Nr1h4-de

SUBMITTER: Mishima Y 

PROVIDER: S-EPMC12332403 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature