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

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Science  23 Feb 1996:
Vol. 271, Issue 5252, pp. 1126-1128
DOI: 10.1126/science.271.5252.1126


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.

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