The canalicular multispecific organic anion transporter and conjugated hyperbilirubinemia in rat and man.
The human Dubin-Johnson syndrome is an autosomal recessive liver disease characterized by a chronic conjugated hyperbilirubinemia. Patients have impaired hepatobiliary transport of many endogenous and xenobiotic compounds. A similar disease phenotype has been described for a naturally occurring mutant Wistar rat strain, the TR- rat, which is defective in the, functionally defined, canalicular multispecific organic anion transporter (cMOAT). The complementary DNA encoding this protein has been cloned from rat and recently from human liver. cMOAT is a new member of the ATP-binding cassette transporter family, and homologous to the multidrug resistance-associated protein 1. A mutation in the cMOAT gene is responsible for the phenotype observed in TR- rats. This information should soon lead tc a complete genetic characterization of the human Dubin-Johnson syndrome.
Paulusma
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CC
Department of Gastrointestinal and Liver Diseases, Center for Liver and Intestinal Research, Academic Medical Center, Amsterdam, The Netherlands.
Oude Elferink
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D000818:Animals; D027321:Anion Transport Proteins; D001647:Bile Acids and Salts / Q000378:metabolism*; D001648:Bile Canaliculi / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018076:DNA, Complementary / Q000302:isolation & purification; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases; D006932:Hyperbilirubinemia / Q000378:metabolism*; D007566:Jaundice, Chronic Idiopathic / Q000378:metabolism*; D008562:Membrane Glycoproteins; D051381:Rats; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)
D027321:Anion Transport Proteins; D001647:Bile Acids and Salts; D002352:Carrier Proteins; D018076:DNA, Complementary; D006913:Hydroxysteroid Dehydrogenases; D008562:Membrane Glycoproteins; C037643:bile acid binding proteins; C435496:AKR1C2 protein, human; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)