PMID- 10464142
OWN - NLM
STAT- MEDLINE
DCOM- 19990916
LR  - 20211203
IS  - 0016-5085 (Print)
IS  - 0016-5085 (Linking)
VI  - 117
IP  - 3
DP  - 1999 Sep
TI  - Exon-intron organization of the human multidrug-resistance protein 2 (MRP2) gene 
      mutated in Dubin-Johnson syndrome.
PG  - 653-60
AB  - BACKGROUND & AIMS: The Dubin-Johnson syndrome is characterized by conjugated 
      hyperbilirubinemia and by impaired secretion of anionic conjugates from 
      hepatocytes into bile. Absence of the multidrug-resistance protein 2 (MRP2; 
      symbol ABCC2), an adenosine triphosphate-dependent conjugate export pump, from 
      the hepatocyte canalicular membrane is the molecular basis of this syndrome. The 
      aim of this study was the elucidation of all exon-intron boundaries of the MRP2 
      gene as a prerequisite for the analysis of mutations in patients with 
      Dubin-Johnson syndrome. METHODS: Exon-intron boundaries of MRP2 were determined, 
      and the amplified exons were screened for mutations. Immunofluorescence 
      microscopy served to localize the MRP2 protein in human liver. RESULTS: The human 
      MRP2 gene is approximately 45 kilobases long; it contains 32 exons and a high 
      proportion of class 0 introns. In 2 patients with Dubin-Johnson syndrome, we 
      detected a nonsense mutation at codon 1066 and a 6-nucleotide deletion mutation 
      affecting codons 1392-1394. The MRP2 protein was absent from the canalicular 
      membrane of both patients. CONCLUSIONS: The mutations detected so far show that 
      various mutations in the MRP2 gene can lead to the Dubin-Johnson syndrome. The 
      exon-intron boundaries established in this article will facilitate the analysis 
      of additional mutations in the MRP2 gene.
FAU - Tsujii, H
AU  - Tsujii H
AD  - Division of Tumor Biochemistry, Deutsches Krebsforschungszentrum, Heidelberg, 
      Germany.
FAU - Konig, J
AU  - Konig J
FAU - Rost, D
AU  - Rost D
FAU - Stockel, B
AU  - Stockel B
FAU - Leuschner, U
AU  - Leuschner U
FAU - Keppler, D
AU  - Keppler D
LA  - eng
SI  - GENBANK/AJ132244
SI  - GENBANK/AJ132287
SI  - GENBANK/AJ132288
SI  - GENBANK/AJ132289
SI  - GENBANK/AJ132290
SI  - GENBANK/AJ132291
SI  - GENBANK/AJ132292
SI  - GENBANK/AJ132293
SI  - GENBANK/AJ132294
SI  - GENBANK/AJ132295
SI  - GENBANK/AJ132296
SI  - GENBANK/AJ132297
SI  - GENBANK/AJ132298
SI  - GENBANK/AJ132299
SI  - GENBANK/AJ132300
SI  - GENBANK/AJ132301
SI  - GENBANK/AJ132302
SI  - GENBANK/AJ132303
SI  - GENBANK/AJ132304
SI  - GENBANK/AJ132305
SI  - GENBANK/AJ132306
SI  - GENBANK/AJ132307
SI  - GENBANK/AJ132308
SI  - GENBANK/AJ132309
SI  - GENBANK/AJ132310
SI  - GENBANK/AJ132311
SI  - GENBANK/AJ132312
SI  - GENBANK/AJ132313
SI  - GENBANK/AJ132314
SI  - GENBANK/AJ245625
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Gastroenterology
JT  - Gastroenterology
JID - 0374630
RN  - 0 (ABCC2 protein, human)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Multidrug Resistance-Associated Protein 2)
RN  - 0 (Multidrug Resistance-Associated Proteins)
RN  - Y49M64GZ4Q (multidrug resistance-associated protein 1)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B/*genetics/metabolism
MH  - Adult
MH  - Amino Acid Sequence
MH  - DNA Mutational Analysis
MH  - Exons
MH  - Female
MH  - *Genes, MDR
MH  - Humans
MH  - Introns
MH  - Jaundice, Chronic Idiopathic/*genetics/metabolism
MH  - Liver/metabolism
MH  - *Membrane Transport Proteins
MH  - Microscopy, Fluorescence
MH  - Molecular Sequence Data
MH  - Multidrug Resistance-Associated Protein 2
MH  - *Multidrug Resistance-Associated Proteins
MH  - Mutation
EDAT- 1999/08/28 00:00
MHDA- 1999/08/28 00:01
CRDT- 1999/08/28 00:00
PHST- 1999/08/28 00:00 [pubmed]
PHST- 1999/08/28 00:01 [medline]
PHST- 1999/08/28 00:00 [entrez]
AID - S0016508599002619 [pii]
AID - 10.1016/s0016-5085(99)70459-2 [doi]
PST - ppublish
SO  - Gastroenterology. 1999 Sep;117(3):653-60. doi: 10.1016/s0016-5085(99)70459-2.