The multidrug resistance and cystic fibrosis genes have complementary patterns of epithelial expression.
The cystic fibrosis gene product, CFTR, and the multidrug resistance P-glycoprotein (encoded by the MDR1 gene) are structurally related proteins and both are associated with epithelial chloride channel activities. We have compared their cell-specific expression in the rat by in situ hybridization. In all tissues examined the two genes were found to have complementary patterns of expression, demonstrating exquisite regulation in both cell-specific and temporal fashions. Additionally, a switch in expression from one gene to the other was observed in certain tissues. For example, expression in the intestine switches from CFTR to MDR1 as the cells migrate across the crypt-villus boundary. A switch from CFTR to MDR1 expression was also observed in the uterine epithelium upon pregnancy. These data suggest that CFTR and P-glycoprotein serve analogous roles in epithelial cells and provide additional evidence that P-glycoprotein has a physiological role in regulating epithelial cell volume. The patterns of expression suggest that the regulation of these two genes is coordinately controlled.
Trezise
A E
AE
Department of Genetics, Hospital for Sick Children, Toronto, Ontario, Canada.
Romano
P R
PR
Gill
D R
DR
Hyde
S C
SC
Sepúlveda
F V
FV
Buchwald
M
M
Higgins
C F
CF
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000818:Animals; D001483:Base Sequence; D018118:Chloride Channels; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004351:Drug Resistance / Q000235:genetics*; D005314:Embryonic and Fetal Development / Q000235:genetics; D004848:Epithelium / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D017403:In Situ Hybridization; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D015347:RNA Probes; D051381:Rats; D017208:Rats, Wistar; D013737:Testis / Q000378:metabolism; D014599:Uterus / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018118:Chloride Channels; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D015347:RNA Probes; D019005:Cystic Fibrosis Transmembrane Conductance Regulator