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

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.