Congenital Jaundice in Rats with a Mutation in a Multidrug Resistance-Associated Protein Gene
Coen C. Paulusma(Amsterdam UMC Location University of Amsterdam), Piter J. Bosma(Amsterdam UMC Location University of Amsterdam), Guido J.R. Zaman(Oncode Institute), Conny Bakker(Amsterdam UMC Location University of Amsterdam), M. Ya. Otter(Amsterdam UMC Location University of Amsterdam), George L. Scheffer(University of Amsterdam), Rik J. Scheper(University of Amsterdam), Piet Borst(Oncode Institute), Ronald P.J. Oude Elferink(Amsterdam UMC Location University of Amsterdam)
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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.
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