Atp8b1 deficiency in mice reduces resistance of the canalicular membrane to hydrophobic bile salts and impairs bile salt transport

• DOI: 10.1002/hep.21212
• Publication Date: 2006-06-27T07:26:57Z
• Authors: Coen C. Paulusma; Annemiek Groen; Cindy Kunne; Kam S. Ho-Mok; Astrid L. Spijker...; Rudi D. de Waart; Frans J. Hoek; Heleen Vreeling; Kees A. Hoeben; Jan van Marle; Ludmila Pawlikowska; Laura N. Bull; Alan F. Hofmann; A. S. Knisely; Ronald P. J. Oude...
• Keywords: Adenosine Triphosphatases; Male; 0301 basic medicine; Bile Canaliculi; Blotting, Western; Cell Membrane; Biological Transport; Cholestasis, Intrahepatic; In Vitro Techniques; Immunohistochemistry; Bile Acids and Salts; Disease Models, Animal; Mice; Microscopy, Electron; 03 medical and health sciences; Animals; Chromatography, Thin Layer; Phospholipid Transfer Proteins; Hydrophobic and Hydrophilic Interactions

Progressive familial intrahepatic cholestasis type 1 (PFIC1, Byler disease, OMIM 211600) is a severe inherited liver disease caused by mutations in ATP8B1 . member of the 4 subfamily P-type ATPases, which are phospholipid flippases. PFIC1 patients generally develop end-stage before second decade life. The characterized impaired biliary bile salt excretion, but mechanism whereby function results unclear. In mouse model for PFIC1, we observed decreased resistance hepatocanalicular membrane to hydrophobic salts as evidenced enhanced recovery phosphatidylserine, cholesterol, and ectoenzymes. specimens from patients, not those control subjects, ectoenzyme expression at canalicular was markedly deficient. isolated livers Atp8b1 deficiency transport into bile. conclusion , our study shows that causes loss asymmetry turn renders less resistant toward salts. may subsequently impair cause cholestasis. Supplementary material this article can be found on HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html).