Premium
Defect of multidrug‐resistance 3 gene expression in a subtype of progressive familial intrahepatic cholestasis
Author(s) -
Deleuze J,
Jacquemin E,
Dubuisson C,
Cresteil D,
Dumont M,
Erlinger S,
Bernard O,
Hadchouel M
Publication year - 1996
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510230435
Subject(s) - progressive familial intrahepatic cholestasis , cholestasis , multidrug resistance associated protein 2 , p glycoprotein , biology , multiple drug resistance , phospholipid , messenger rna , medicine , gene , microbiology and biotechnology , endocrinology , genetics , atp binding cassette transporter , transporter , drug resistance , transplantation , membrane , liver transplantation
Disruption of the murine mdr 2 (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 mdr 2 gene expression ( mdr 2 ‐/‐ mice). No mdr 3 (human mdr 2 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 mdr 3 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.