CONGENITAL JAUNDICE IN RATS WITH A MUTATION IN A MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN GENE

The human Dubin-Johnson syndrome and its animal model, the TR(-) rat, are characterized by a chronic conjugated hyperbilirubinemia. TR(-) ra ts are defective in the canalicular multispecific organic anion transp orter (cMOAT), which mediates hepatobiliary excretion of numerous orga nic anions. The complementary DNA for rat cmoat, a homolog of the huma n multidrug resistance gene (hMRP1), was isolated and shown to be expr essed in the canalicular membrane of hepatocytes. In the TR(-) rat, a single-nucleotide deletion in this gene resulted in a reduced messenge r RNA level and absence of the protein. It is likely that this mutatio n accounts for the TR(-) phenotype.