Congenital jaundice in rats with a mutation in a multidrug resistance-associated protein gene

C. C. Paulusma; P. J. Bosma; G. J. Zaman; C. T. Bakker; M. Otter; G. L. Scheffer; R. J. Scheper; P. Borst; R. P. Oude Elferink

doi:https://doi.org/10.1126/science.271.5252.1126

Congenital jaundice in rats with a mutation in a multidrug resistance-associated protein gene

C. C. Paulusma, P. J. Bosma, G. J. Zaman, C. T. Bakker, M. Otter, G. L. Scheffer, R. J. Scheper, P. Borst, R. P. Oude Elferink

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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

Original language	English
Pages (from-to)	1126-1128
Journal	Science
Volume	271
Issue number	5252
DOIs	https://doi.org/10.1126/science.271.5252.1126
Publication status	Published - 1996

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https://doi.org/10.1126/science.271.5252.1126

Cite this

@article{13c2d66fa68b4c57996b7f5ee475235e,

title = "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",

author = "Paulusma, {C. C.} and Bosma, {P. J.} and Zaman, {G. J.} and Bakker, {C. T.} and M. Otter and Scheffer, {G. L.} and Scheper, {R. J.} and P. Borst and {Oude Elferink}, {R. P.}",

year = "1996",

doi = "https://doi.org/10.1126/science.271.5252.1126",

language = "English",

volume = "271",

pages = "1126--1128",

journal = "Science",

issn = "0036-8075",

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TY - JOUR

T1 - Congenital jaundice in rats with a mutation in a multidrug resistance-associated protein gene

AU - Paulusma, C. C.

AU - Bosma, P. J.

AU - Zaman, G. J.

AU - Bakker, C. T.

AU - Otter, M.

AU - Scheffer, G. L.

AU - Scheper, R. J.

AU - Borst, P.

AU - Oude Elferink, R. P.

PY - 1996

Y1 - 1996

N2 - 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

AB - 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

U2 - https://doi.org/10.1126/science.271.5252.1126

DO - https://doi.org/10.1126/science.271.5252.1126

M3 - Article

C2 - 8599091

SN - 0036-8075

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EP - 1128

JO - Science

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