Defect of multidrug-resistance 3 gene expression in a subtype of progressive familial intrahepatic cholestasis

Hepatology. 1996 Apr;23(4):904-8. doi: 10.1002/hep.510230435.

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • ATP-Binding Cassette Transporters / genetics*
  • Animals
  • Child, Preschool
  • Cholestasis, Intrahepatic / genetics
  • Cholestasis, Intrahepatic / metabolism*
  • Drug Resistance, Multiple / genetics*
  • Female
  • Gene Expression
  • Humans
  • Mice
  • RNA, Messenger / analysis*
  • gamma-Glutamyltransferase / blood

Substances

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP-Binding Cassette Transporters
  • RNA, Messenger
  • multidrug resistance protein 3
  • gamma-Glutamyltransferase