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Institut National de la Santé et de la Recherche Médicale U478, Federative Institute of Research 02, Bichat Medical School, 75870 Paris Cedex 18, France
First published August
30, 2001; 10.1152/ajprenal.00360.2000.
The renal collecting duct
(CD) plays a key role in the control of ion and fluid homeostasis.
Several genetic diseases that involve mutations in genes encoding for
ion transporters or hormone receptors specifically expressed in CD have
been described. Suitable cellular or transgenic animal models
expressing such mutated genes in an inducible manner should represent
attractive systems for structure-function relationship analyses and the
generation of appropriate physiopathological models of related
diseases. Our first goal was to develop a CD cell line that allows
inducible gene expression using the tetracycline-inducible system
(Tet-On). We designed several strategies aimed at the development of a
tight and highly inducible system in RCCD1 cells, a rat cortical collecting duct (CCD) cell line exhibiting several properties of the
native CCD. Analysis of reporter gene expression demonstrated that the
Tet-On system is suitable for inducible gene expression in these cells.
In a second step, we have tested whether transgenic Tet-On mice
expressing the tetracycline transactivator under the control of the
human cytomegalovirus promoter were suitable for inducible gene
expression in tubule epithelial cells. The results indicate that, in
vivo, the inducible expression of the lacZ reporter gene
appeared to be restricted to the CD. This particular strain of
transgenic mice may therefore be useful for the expression of genes of
interest in an inducible manner in the collecting duct.
transgenic; inducible systems; conditional systems; kidney; physiopathology
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