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Defect of multidrug-resistance 3 gene expression in a subtype of progressive familial intrahepatic cholestasis.
Hepatology : Official Journal of the American Association for the Study of Liver Diseases 1996 April
Disruption of the murine mdr2 (multidrug-resistance) gene, which encodes a phosphatidylcholine flippase, leads to a hepatic disorder because of loss of biliary phospholipid secretion. Among the hereditary human cholestasis, a subtype of progressive familial intrahepatic cholestasis with high gamma-glutamyltranspeptidase (GGT) serum activity shares histological, biochemical, and genetic features with mice lacking mdr2 gene expression (mdr2 -/- mice). No MDR3 (human mdr2 homolog) messenger RNA (mRNA) was detected by Northern blotting in the liver of a patient suffering from this form of PFIC, and the biliary phospholipid level in a second patient was substantially decreased. Thus, the absence of the MDR3 P-glycoprotein may be responsible for this type of PFIC, which, as in the murine model, may be due to a toxic effect of bile acids on the biliary epithelium in absence of biliary phospholipids.
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