The canalicular multispecific organic anion transporter and conjugated hyperbilirubinemia in rat and man

Abstract

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 anton 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 ob served in TR rats. This information should soon lead to a complete genetic characterization of the human Dubin Johnson syndrome.