title: Liver diseases related to MDR3 (ABCB4) gene deficiency.
abstract: Class III multidrug resistance P-glycoproteins, mdr2 in mice and MDR3 in human, are canalicular phospholipid translocators involved in biliary phospholipid (phosphatidylcholine) excretion.The role of a MDR3 (ABCB4) gene defect in liver disease has been initially proven in a subtype of progressive familial intrahepatic cholestasis called PFIC3, a severe pediatric liver disease that may require liver transplantation.Several MDR3 mutations have been identified in children with PFIC3 and are associated to low level of phospholipids in bile leading to high biliary cholesterol saturation index.MDR3 mutations are associated to loss of canalicular MDR3 protein and /or to loss of protein function.There is evidence that biallelic or monoallelic MDR3 defect causes or predisposes to 6 human liver diseases (PFIC3, adult biliary cirrhosis, low phospholipid associated cholelithiasis syndrome, transient neonatal cholestasis, intrahepatic cholestasis of pregnancy, drug induced cholestasis).Some patients with MDR3 deficiency may benefit from ursodeoxycholic acid therapy and could be good candidates to a targeted pharmacological approach and/or to cell therapy in the future.
authors.affiliation: Pediatric Hepatology and National Reference Centre for Biliary Atresia, Bicêtre Hospital, University of Paris - South 11, AP-HP, Paris, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Gonzales
authors.forename: Anne
authors.initials: A
authors.lastname: Davit-Spraul
authors.forename: Christiane
authors.initials: C
authors.lastname: Baussan
authors.forename: Catherine
authors.initials: C
authors.lastname: Buffet
authors.forename: Michele
authors.initials: M
authors.lastname: Maurice
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Jacquemin
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics*; D000818:Animals; D001659:Biliary Tract / Q000378:metabolism; D005838:Genotype; D006801:Humans; D008107:Liver Diseases / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D010743:Phospholipids / Q000378:metabolism
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D010743:Phospholipids; C095122:multidrug resistance protein 3