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.
MeSH terms
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ATP-Binding Cassette Transporters / analysis
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ATP-Binding Cassette Transporters / chemistry
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ATP-Binding Cassette Transporters / genetics*
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Amino Acid Sequence
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Animals
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Anion Transport Proteins
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Base Sequence
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Carrier Proteins / analysis
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Carrier Proteins / chemistry
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Carrier Proteins / genetics*
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Cell Membrane / chemistry
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DNA, Complementary / genetics
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Frameshift Mutation
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Humans
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Hyperbilirubinemia, Hereditary / genetics*
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Liver / chemistry*
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Liver / cytology
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Molecular Sequence Data
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Molecular Weight
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Multidrug Resistance-Associated Proteins
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Phenotype
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Rats
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Rats, Wistar
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Sequence Alignment
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Sequence Deletion
Substances
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ATP-Binding Cassette Transporters
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Anion Transport Proteins
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Carrier Proteins
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DNA, Complementary
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Multidrug Resistance-Associated Proteins