Slc10a1, encoding the sodium-taurocholate cotransporting polypeptide (NTCP), is a crucial basolateral (sinusoidal) Na+-bile acid co-transporter. It mediates the hepatic uptake of bile acids, and is also the receptor for hepatitis B and D viruses. Additionally, it serves as a transporter for some drugs and is involved in multiple biological processes related to bile acid metabolism and virus-host interactions [1,2,4,5].

In gene-knockout studies, Slc10a1-knockout (Slc10a1-/-) mice had substantially increased serum bile acid (BA) levels compared to wild-type mice, indicating its key role in BA uptake. The increase was attenuated in Slc10a1hSLCO1B3-mice, suggesting that OATP1B3 can partially compensate for the function of NTCP in BA uptake. Also, TCA-induced bile flow was significantly impaired in Slc10a1-/-mice but partially recovered in Slc10a1hSLC01B3-mice [3]. In terms of disease-related findings, the SLC10A1 Ser267Phe (S267F) variant severely inhibits HBV infection and taurocholate transport activity. Subjects with the AA genotype of SLC10A1 may escape HBV infection and have decreased cholesterol levels due to impaired bile acid uptake. The rs2296651 genotypes of SLC10A1 also have pleiotropic effects on biochemical traits, HBV infection susceptibility, and the risk of gallstone disease [1,2].

In conclusion, Slc10a1 is essential for bile acid uptake in the liver. Gene-knockout mouse models have revealed its significance in maintaining normal bile acid levels and its role in HBV infection and related metabolic processes. Understanding Slc10a1 through these models provides insights into diseases such as HBV-related liver diseases, gallstone disease, and conditions related to abnormal bile acid metabolism.

References:

1. Cheng, Xiang, Wang, Ying, Tian, Jianbo, Liu, Li, Zhong, Rong. 2019. SLC10A1 S267F variant influences susceptibility to HBV infection and reduces cholesterol level by impairing bile acid uptake. In Journal of viral hepatitis, 26, 1178-1185. doi:10.1111/jvh.13157. https://pubmed.ncbi.nlm.nih.gov/31177598/

2. Ko, Yu-Lin, Tuan, Wei-Lun, Teng, Ming-Sheng, Wu, Semon, Hsu, Lung-An. 2024. SLC10A1 rs2296651 variant (S267F mutation) predicts biochemical traits, hepatitis B virus infection susceptibility and the risk of gallstone disease. In Molecular genetics and genomics : MGG, 299, 62. doi:10.1007/s00438-024-02153-2. https://pubmed.ncbi.nlm.nih.gov/38869622/

3. Pan, Qiong, Zhu, Guanyu, Xu, Ziqian, Boyer, James L, Chai, Jin. 2023. Organic Anion Transporting Polypeptide (OATP) 1B3 is a Significant Transporter for Hepatic Uptake of Conjugated Bile Acids in Humans. In Cellular and molecular gastroenterology and hepatology, 16, 223-242. doi:10.1016/j.jcmgh.2023.04.007. https://pubmed.ncbi.nlm.nih.gov/37146714/

4. Deng, Li-Jing, Ouyang, Wen-Xian, Liu, Rui, Li, Shuang-Jie, Song, Yuan-Zong. 2021. Clinical characterization of NTCP deficiency in paediatric patients : A case-control study based on SLC10A1 genotyping analysis. In Liver international : official journal of the International Association for the Study of the Liver, 41, 2720-2728. doi:10.1111/liv.15031. https://pubmed.ncbi.nlm.nih.gov/34369070/

5. Liu, Ruihong, Chen, Chuming, Xia, Xuefeng, Peng, Liang, Wang, Yiming. 2017. Homozygous p.Ser267Phe in SLC10A1 is associated with a new type of hypercholanemia and implications for personalized medicine. In Scientific reports, 7, 9214. doi:10.1038/s41598-017-07012-2. https://pubmed.ncbi.nlm.nih.gov/28835676/