Regional variations in ABC transporter expression along the mouse intestinal tract.
The ATP-binding cassette (ABC) family of proteins comprise a group of membrane transporters involved in the transport of a wide variety of compounds, such as xenobiotics, vitamins, lipids, amino acids, and carbohydrates. Determining their regional expression patterns along the intestinal tract will further characterize their transport functions in the gut. The mRNA expression levels of murine ABC transporters in the duodenum, jejunum, ileum, and colon were examined using the Affymetrix MuU74v2 GeneChip set. Eight ABC transporters (Abcb2, Abcb3, Abcb9, Abcc3, Abcc6, Abcd1, Abcg5, and Abcg8) displayed significant differential gene expression along the intestinal tract, as determined by two statistical models (a global error assessment model and a classic ANOVA, both with a P < 0.01). Concordance with semiquantitative real-time PCR was high. Analyzing the promoters of the differentially expressed ABC transporters did not identify common transcriptional motifs between family members or with other genes; however, the expression profile for Abcb9 was highly correlated with fibulin-1, and both genes share a common complex promoter model involving the NFkappaB, zinc binding protein factor (ZBPF), GC-box factors SP1/GC (SP1F), and early growth response factor (EGRF) transcription binding motifs. The cellular location of another of the differentially expressed ABC transporters, Abcc3, was examined by immunohistochemistry. Staining revealed that the protein is consistently expressed in the basolateral compartment of enterocytes along the anterior-posterior axis of the intestine. Furthermore, the intensity of the staining pattern is concordant with the expression profile. This agrees with previous findings in which the mRNA, protein, and transport function of Abcc3 were increased in the rat distal intestine. These data reveal regional differences in gene expression profiles along the intestinal tract and demonstrate that a complete understanding of intestinal ABC transporter function can only be achieved by examining the physiologically distinct regions of the gut.
Mutch
David M
DM
Nestlé Research Center, CH-1000 Lausanne 26, Switzerland.
Anderle
Pascale
P
Fiaux
Muriel
M
Mansourian
Robert
R
Vidal
Karine
K
Wahli
Walter
W
Williamson
Gary
G
Roberts
Matthew-Alan
MA
D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D000818:Animals; D003106:Colon / Q000737:chemistry / Q000378:metabolism; D003199:Computer Systems; D018076:DNA, Complementary / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods / Q000706:statistics & numerical data / Q000662:veterinary; D014644:Genetic Variation / Q000235:genetics*; D007150:Immunohistochemistry / Q000379:methods / Q000662:veterinary; D007413:Intestinal Mucosa / Q000737:chemistry / Q000378:metabolism*; D007421:Intestine, Small / Q000737:chemistry / Q000378:metabolism; D007422:Intestines / Q000737:chemistry*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods / Q000706:statistics & numerical data / Q000662:veterinary; D016133:Polymerase Chain Reaction / Q000379:methods / Q000706:statistics & numerical data / Q000662:veterinary; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis
D018528:ATP-Binding Cassette Transporters; D018076:DNA, Complementary; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger; C114462:multidrug resistance-associated protein 3