Congenital Jaundice in Rats with a Mutation in a Multidrug Resistance-Associated Protein Gene

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Abstract
The human Dubin-Johnson syndrome and its animal model, the TR− rat, are characterized by a chronic conjugated hyperbilirubinemia. TR− rats are defective in the canalicular multispecific organic anion transporter (cMOAT), which mediates hepatobiliary excretion of numerous organic anions. The complementary DNA for rat cmoat, a homolog of the human multidrug resistance gene (hMRP1), was isolated and shown to be expressed in the canalicular membrane of hepatocytes. In the TR− rat, a single-nucleotide deletion in this gene resulted in a reduced messenger RNA level and absence of the protein. It is likely that this mutation accounts for the TR− phenotype.