| First Author | Van Nieuwkerk CM | Year | 1996 |
| Journal | Gastroenterology | Volume | 111 |
| Issue | 1 | Pages | 165-71 |
| PubMed ID | 8698195 | Mgi Jnum | J:34646 |
| Mgi Id | MGI:82101 | Doi | 10.1053/gast.1996.v111.pm8698195 |
| Citation | Van Nieuwkerk CM, et al. (1996) Effects of Ursodeoxycholate and cholate feeding on liver disease in FVB mice with a disrupted mdr2 P-glycoprotein gene. Gastroenterology 111(1):165-71 |
| abstractText | BACKGROUND & AIMS: The mouse mdr2 gene encodes a P-glycoprotein expressed in the hepatocanalicular membrane. Inactivation of this gene causes lack of biliary phospholipid and cholesterol secretion and non-suppurative cholangitis. The aim of this study was to investigate the role of bile salt hydrophobicity in induction of liver pathology in mdr2 (-/-) mice. METHODS: Mice (+/+) wild type or (-/-) knockout for the mdr2 gene were fed with either purified control diet or this diet supplemented with cholate (0.1%) or ursodeoxycholate (0.5%) for 3, 6, or 22 weeks after weaning. Liver histology was semiquantitatively scored. RESULTS: Each mouse fed bile acid became the major constituent of the bile salt pool. The cholate diet during 22 weeks induced only very mild liver pathology in (+/+) mice. By contrast, lever histology had already deteriorated after 3 weeks in the (-/-) mice and caused pronounced inflammatory nonsuppurative cholangitis and fibrosis in the 75% of mice that survived. Dietary ursodeoxycholate had no effect on histology in (+/+) mice but improved liver pathology significantly in (-/-) mice compared with purified control diet; the decrease of ductular proliferation and portal inflammation was most prominent after 22 weeks. CONCLUSIONS: The cholangiolitis and its sequelae in the mdr2 knockout mice depend on bile salt hydrophobicity. |
