Caractérisation et étude d'un élément régulateur du gène codant pour le récepteur à la vasopressine de type 2

Abstract : Transcriptional control is the primary means of regulating genes expression in eukaryotes cells. The laboratory identified six independent families with X-linked nephrogenic diabete insipidus (NDI) bearing large deletions upstream of the AVPR2 gene leaving intact AVPR2 and AQP2 coding sequences. Males bearing these deletions have classical renal X-linked NDI. The sequencing and analysis of 61 kilo bases upstream and downstream encompassing the AVPR2 gene had led to identify 6 deletions in 6 ancestrally independent families including, 5 larger than 7 kilo bases and one of 102 base paires shared by the other deletions. In male patient bearing the 102 bp upstream deletion, V2 receptors are not expressed in renal collecting duct cells but normally expressed in endothelial cells. Our goal is thus to understand the regulatory mechanism controlling the AVPR2 locus and more precisely the tissu specific expression of this gene. The studies carried out in the Hprt system, confirm the enhancer role of the sequence of 102 bp. In vitro undertaken experiments indicate that this effect depends on the extracellular context, of the nature of the cells, as well as promoter of the AVPR2. The identification of proteins potentially binding one of the ends of the deletion revealed the presence, either of regulating proteins, or of unknown sequences, all expressed in the kidney. In the long term, these studies, like those while rising, will make it possible to position the AVPR2 gene like a target of choice in the treatment of the diabetes insipidus, central and nephrogenic, by genic therapy.
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Contributor : Nicolas Debrand <>
Submitted on : Friday, May 21, 2010 - 3:52:14 PM
Last modification on : Wednesday, April 17, 2019 - 12:15:34 PM
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  • HAL Id : tel-00485725, version 1


Nicolas Debrand. Caractérisation et étude d'un élément régulateur du gène codant pour le récepteur à la vasopressine de type 2. Biochimie [q-bio.BM]. Université de Montréal; Université Pierre et Marie Curie - Paris VI, 2008. Français. ⟨tel-00485725⟩



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