Prion Replication in the Hematopoietic Compartment Is Not Required for Neuroinvasion in Scrapie Mouse Model |
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| Authors: | Corinne Loeuillet Catherine Lemaire-Vieille Philippe Naquet Marie-France Cesbron-Delauw Jean Gagnon Jean-Yves Cesbron |
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| Institution: | 1. Laboratoire Adaptation et Pathogénie des Micro-organismes, Centre National Recherche Scientifique UMR 5163, Université Joseph Fourier, Grenoble, France.; 2. Centre d''Immunologie de Marseille-Luminy, Institut National de la Santé et de la Recherche Médicale, Centre National Recherche Scientifique, Université de La Méditerranée, Marseille, France.;Universidad de la Republica, Uruguay |
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| Abstract: | Fatal neurodegenerative prion diseases are caused by the transmissible PrPSc prion agent whose initial replication after peripheral inoculation takes place in follicular dendritic cells present in germinal centers of lymphoid organs. However, prion replication also occurs in lymphoid cells. To assess the role of the hematopoietic compartment in neuroinvasion and prion replication, we generated chimeric mice, on a uniform congenic C57/BL6J background, by bone marrow replacement with hematopoietic cells expressing different levels of PrP protein. Nine different types of chimeric mice were inoculated intraperitoneally either with the lymphotropic Rocky Mountain Laboratory (RML) strain or the non lymphotropic ME-7 scrapie strain, at different doses. Here, we clearly demonstrate that overexpression of PrP by the hematopoietic system, or the lack of PrP expression by the bone marrow derived cells, does not change the incubation time period of the disease, even when the mice are infected at limiting doses. We conclude that the hematopoietic compartment is more or less permissive to prion replication, both for RML and ME-7, but does not play a role in neuroinvasion. |
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