Abcb4, also known as multidrug resistance protein 3 (MDR3), is a member of the ATP-binding cassette transporter superfamily. It is localized at the canalicular membrane of hepatocytes and mediates the translocation of phosphatidylcholine (PC) into bile. This function is crucial for solubilizing cholesterol into mixed micelles and preventing bile acid toxicity towards hepatobiliary epithelia, thus protecting the hepatobiliary system [1,2,3,4].

ABCB4 deficiency, often caused by gene mutations, can lead to various liver diseases. In ABCB4 knockout mice, a model for low phospholipid-associated cholelithiasis (LPAC), gallbladder bile has trace amounts of phospholipids, is supersaturated with cholesterol, and shows “anhydrous” cholesterol crystallization, consistent with the pathophysiology of LPAC in humans [5].

In conclusion, Abcb4 is essential for biliary phospholipid secretion, playing a key role in maintaining hepatobiliary health. Studies using ABCB4 knockout mouse models have been instrumental in understanding the pathogenesis of LPAC and potentially other related cholestatic diseases, providing insights into the mechanisms underlying these conditions and potentially guiding future therapeutic strategies [5].

References:

1. Sticova, Eva, Jirsa, Milan. 2019. ABCB4 disease: Many faces of one gene deficiency. In Annals of hepatology, 19, 126-133. doi:10.1016/j.aohep.2019.09.010. https://pubmed.ncbi.nlm.nih.gov/31759867/

2. Prescher, Martin, Kroll, Tim, Schmitt, Lutz. . ABCB4/MDR3 in health and disease - at the crossroads of biochemistry and medicine. In Biological chemistry, 400, 1245-1259. doi:10.1515/hsz-2018-0441. https://pubmed.ncbi.nlm.nih.gov/30730833/

3. Reichert, Matthias Christian, Lammert, Frank. 2018. ABCB4 Gene Aberrations in Human Liver Disease: An Evolving Spectrum. In Seminars in liver disease, 38, 299-307. doi:10.1055/s-0038-1667299. https://pubmed.ncbi.nlm.nih.gov/30357767/

4. Falguières, Thomas, Aït-Slimane, Tounsia, Housset, Chantal, Maurice, Michèle. 2014. ABCB4: Insights from pathobiology into therapy. In Clinics and research in hepatology and gastroenterology, 38, 557-63. doi:10.1016/j.clinre.2014.03.001. https://pubmed.ncbi.nlm.nih.gov/24953525/

5. Wang, Helen H, Portincasa, Piero, Liu, Min, Wang, David Q-H. 2022. Genetic Analysis of ABCB4 Mutations and Variants Related to the Pathogenesis and Pathophysiology of Low Phospholipid-Associated Cholelithiasis. In Genes, 13, . doi:10.3390/genes13061047. https://pubmed.ncbi.nlm.nih.gov/35741809/