Co-Ordinate Regulation of the Cystic Fibrosis and Multidrug Resistance Genes in Cystic Fibrosis Knockout Mice
Authors: Trezise, Ann E. O.; Ratcliff, Rosemary; Hawkins, Tim E.; Evans, Martin J.; Freeman, Tom C.; Romano, Pascale R.; Higgins, Christopher F.; Colledge, William H.
Source: Human Molecular Genetics, Volume 6, Number 4, 1997 , pp. 527-537(11)
Publisher: Oxford University Press
Abstract: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 (Cftrtm1CAM ). Cftr mRNA expression in CftrtmlCAM/CftrtmlCAM mice was 4-fold reduced in the intestine, as compared with littermate wild-type mice. All other CftrtmlCAM/CftrtmlCAM 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 CftrtmlCAM/CftrtmlCAM mice, as compared with age-matched +/+ mice, and an intermediate level of Mdr1 mRNA in heterozygous Cftrtm1CAM mice. In 10-week-old, CftrtmlCAM/CftrtmlCAM 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 CftrtmlCAM/CftrtmlCAM 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.
Document Type: Research Article
Publication date: 1997-01-01
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