1. Volume 117, Issue 3, Pages 653-660 (September 1999)
Exon-intron organization of the human multidrug-resistance protein 2 (MRP2) gene mutated in Dubin–Johnson syndrome 
Hiroyuki Tsujii*, Jörg König*, Daniel Rost*, Birgit Stöckel*, Ulrich Leuschner‡, Dietrich Keppler* 
Gastroenterology 
Volume 117, Issue 3, Pages (September 1999)
DOI: /S (99)
Copyright © 1999 American Gastroenterological Association Terms and Conditions

2. Fig. 1
Exon-intron organization of the human MRP2 gene. (A) Sizes of the exons and introns, phase of the introns, and nucleotide sequences of splice-acceptor and splice-donor sites. Exon and intron sequences are shown in uppercase and lowercase, respectively. The size of introns is estimated from the molecular weight markers and is therefore approximate. (B) Diagrammatic representation of the exon-intron organization of the human MRP2 gene. Exons are numbered and represented by vertical bars; introns are shown as horizontal thin lines. The 5' and 3' untranslated regions (5'UTR and 3'UTR), the location of the start codon ATG (in exon 1), and the termination codon TAG (in exon 32) are indicated.
Gastroenterology  , DOI: ( /S (99) )
Copyright © 1999 American Gastroenterological Association Terms and Conditions

3. Fig. 2
Diagram illustrating components of the MRP2 mRNA and the sites of mutations in Dubin–Johnson syndrome. Exon numbers are indicated, and exon boundaries are represented by vertical lines. The nucleotide-binding domains (NBD1 and NBD2) are marked by shaded boxes. Arrows at top indicate sites of mutations in the MRP2 gene identified at present. F1–3 correspond to mutations reported by the Fukuoka group,13 H1 and 2 to our Heidelberg study (Figure 3), and A1 to the patient studied in Amsterdam.10
Gastroenterology  , DOI: ( /S (99) )
Copyright © 1999 American Gastroenterological Association Terms and Conditions

4. Fig. 3
Partial MRP2 genomic DNA sequences with different mutations in 2 individuals with Dubin–Johnson syndrome. (A) Site of the mutation at codon 1066, corresponding to nucleotides 3196–3198 in exon 23. This codon normally encodes an arginine residue (CGA) and is mutated to a stop codon (TGA) in patient H1. (B) Six-nucleotide deletion affecting codons 1392–1394, corresponding to nucleotides 4175–4180 in exon 30. This deletion results in the loss of two amino acids (arginine and methionine) in patient H2.
Gastroenterology  , DOI: ( /S (99) )
Copyright © 1999 American Gastroenterological Association Terms and Conditions

5. Fig. 4
Expression of P-glycoproteins (P-Gps) and MRP2 in (A, B, and C) normal and (D, E, and F) Dubin–Johnson syndrome liver. Double-label immunofluorescence microscopy was performed as described in Materials and Methods. In control liver, P-glycoproteins (A; green) and MRP2 (B; red) colocalize to the canalicular membrane domain, resulting in a yellow color (C). In patient H2 with Dubin–Johnson syndrome, immunofluorescence microscopy reveals the complete absence of MRP2 from the hepatocyte canalicular membrane as well as other membrane domains (E and F). Expression of P-glycoproteins, however, is not affected in the patient (D and F). Open arrowheads indicate the autofluorescence of pigment granules typically observed in Dubin–Johnson syndrome liver. These pigment granules do not contain MRP2 protein (bar in C = 10 μm; same original magnification in all panels).
Gastroenterology  , DOI: ( /S (99) )
Copyright © 1999 American Gastroenterological Association Terms and Conditions

6. Fig. 5
Alignment of the amino acid sequences of human MRP117,20 and human MRP28,12,15 (EMBL/GenBank accessions L05628 and X96395, respectively) showing the location and class of the splice junctions in the corresponding genes. The location (|) and class (0, 1, or 2) of each splice junction are marked above or below the sequence. Locations where splice junctions are conserved are boxed.
Gastroenterology  , DOI: ( /S (99) )
Copyright © 1999 American Gastroenterological Association Terms and Conditions