In vivo mouse models to study bile acid synthesis and signaling

The synthesis of bile acids (BAs) is carried out by complex pathways characterized by sequential chemical reactions in the liver through various cytochromes P450 (CYP) and other enzymes. Maintaining the integrity of these pathways is crucial for normal physiological function in mammals, encompassing hepatic and neurological processes. Studying on the deficiencies in BA synthesis genes offers valuable insights into the significance of BAs in modulating farnesoid X receptor (FXR) signaling and metabolic homeostasis. By creating mouse knockout (KO) models, researchers can manipulate deficiencies in genes involved in BA synthesis, which can be used to study human diseases with BA dysregulation. These KO mouse models allow for a more profound understanding of the functions and regulations of genes responsible for BA synthesis. Furthermore, KO mouse models shed light on the distinct characteristics of individual BA and their roles in nuclear receptor signaling. Notably, alterations of BA synthesis genes in mouse models have distinct differences when compared to human diseases caused by the same BA synthesis gene deficiencies. This review summarizes several mouse KO models used to study BA synthesis and related human diseases, including mice deficient in Cyp7a1, Cyp27a1, Cyp7a1/Cyp27a1, Cyp8b1, Cyp7b1, Cyp2c70, Cyp2a12, and Cyp2c70/Cyp2a12, as well as germ-free mice. (c) 2023 First Affiliated Hospital, Zhejiang University School of Medicine in China.