Congenital jaundice in rats with a mutation in a multidrug resistance-associated protein gene.
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.
Paulusma
C C
CC
Department of Gastrointestinal and Liver Diseases, Center for Liver and Intestinal Research, Academic Medical Center, Amsterdam, Netherlands.
Bosma
P J
PJ
Zaman
G J
GJ
Bakker
C T
CT
Otter
M
M
Scheffer
G L
GL
Scheper
R J
RJ
Borst
P
P
Oude Elferink
R P
RP
D018528:ATP-Binding Cassette Transporters / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D027321:Anion Transport Proteins; D001483:Base Sequence; D002352:Carrier Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D002462:Cell Membrane / Q000737:chemistry; D018076:DNA, Complementary / Q000235:genetics; D016368:Frameshift Mutation; D006801:Humans; D006933:Hyperbilirubinemia, Hereditary / Q000235:genetics*; D008099:Liver / Q000737:chemistry* / Q000166:cytology; D008969:Molecular Sequence Data; D008970:Molecular Weight; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar; D016415:Sequence Alignment; D017384:Sequence Deletion
D018528:ATP-Binding Cassette Transporters; D027321:Anion Transport Proteins; D002352:Carrier Proteins; D018076:DNA, Complementary; D027425:ATP-Binding Cassette, Sub-Family C Proteins