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Role of PrP in uptake and release of metal ions 2

Our contribution to this task has been to establish cell systems enabling a regulatable expression of PrP as a tool to examine the involvement of this protein in metal ion metabolism, oxidative stress response and signal transduction. One such system (clone A74), has been extensively used by partner 4 to show that expression of PrP increases cellular copper binding and antioxidant activities but not copper delivery (Rachidi et al. J. Biol. Chem. 2003). A74 cells consist of rabbit cells (RK13 line) that have been genetically engineered to express mouse PrP (allele a) under control of a tetracycline-inducible promoter. This cell system is based on the "Rov" cell system previously developed in the laboratory, in which expression of ovine PrP confers permissiveness to infection by sheep prion (Vilette et al PNAS 2001). In the A74 cells, the expression of PrP is tightly regulated, thus providing a relevant model in which the dose-effect relationship between PrP expression and copper binding could be readily assessed.

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