title: Defect of multidrug-resistance 3 gene expression in a subtype of progressive familial intrahepatic cholestasis.
abstract: 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.
authors.affiliation: Unité INSERM U 347, le Kremlin Bicêtre, France.
authors.forename: J F
authors.initials: JF
authors.lastname: Deleuze
authors.forename: E
authors.initials: E
authors.lastname: Jacquemin
authors.forename: C
authors.initials: C
authors.lastname: Dubuisson
authors.forename: D
authors.initials: D
authors.lastname: Cresteil
authors.forename: M
authors.initials: M
authors.lastname: Dumont
authors.forename: S
authors.initials: S
authors.lastname: Erlinger
authors.forename: O
authors.initials: O
authors.lastname: Bernard
authors.forename: M
authors.initials: M
authors.lastname: Hadchouel
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000818:Animals; D002675:Child, Preschool; D002780:Cholestasis, Intrahepatic / Q000235:genetics / Q000378:metabolism*; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis*; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D012333:RNA, Messenger; C095122:multidrug resistance protein 3; D005723:gamma-Glutamyltransferase