Human Molecular Genetics, Vol 6, 527-537, Copyright © 1997 by Oxford University Press
AE Trezise, R Ratcliff, TE Hawkins, MJ Evans, TC Freeman, PR Romano, CF Higgins and WH Colledge
The cystic fibrosis (Cftr and multidrug resistance (Mdr1) genes encode
structurally similar proteins which are members of the ABC transporter
superfamily. These genes exhibit complementary patterns of expression in
vivo, suggesting that the regulation of their expression may be co-
ordinated. We have tested this hypothesis in vivo by examining Cftr and
Mdr1 expression in cystic fibrosis knockout transgenic mice (Cftr(tm1CAM)).
Cftr mRNA expression in Cftr(tm1CAM)/Cftr(tm1CAM) mice was 4-fold reduced
in the intestine, as compared with littermate wild- type mice. All other
Cftr(tm1CAM)/Cftr(tm1CAM) mouse tissues examined showed similar reductions
in Cftr expression. In contrast, we observed a 4-fold increase in Mdr1 mRNA
expression in the intestines of neonatal and 3- to 4-week-old
Cftr(tm1CAM)/Cftr(tm1CAM) mice, as compared with age-matched +/+ mice, and
an intermediate level of Mdr1 mRNA in heterozygous Cftr(tm1CAM) mice. In
10-week-old, Cftr(tm1CAM)/Cftr(tm1CAM) mice and in contrast to the younger
mice, Mdr1 mRNA expression was reduced, by 3-fold. The expression of two
control genes, Pgk-1 and Mdr2, was similar in all genotypes, suggesting
that the changes in Mdr1 mRNA levels observed in the
Cftr(tm1CAM)/Cftr(tm1CAM) mice are specific to the loss of Cftr expression
and/or function. These data provide further evidence supporting the
hypothesis that the regulation Cftr and Mdr1 expression is co-ordinated in
vivo, and that this co-ordinate regulation is influenced by temporal
factors.
ARTICLES
Co-ordinate regulation of the cystic fibrosis and multidrug resistance genes in cystic fibrosis knockout mice
Nuffield Department of Clinical Biochemistry, University of Oxford, John Radcliffe Hospital, UK.
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