NR AUSG
AU Hinske,C.; Sethi,S.K.; Kerksiek,K.; Giese,A.; Wagner,J.; Wagner,I.; Ebner,S.; Brocker,T.; Kretzschmar,H.A.
TI Role of dendritic cells (DC) after oral and intraperitoneal transmission of scrapie
QU TSE-Forum, 6. Kongress - Nationale TSE-Forschungsplattform, Greifswald 26.6.-28.6.2006, Poster: Pathogenese/Infektion PATH-07
PT Konferenz-Poster
AB Controversial results have been observed regarding the role of lymphoid tissues in prion pathogenesis. In order to study the role of dendritic cells (DC) in scrapie pathogenesis we used a novel mouse model. Transgenic CD11c-N17Rac1 mice express a dominant negative variant of Rac-1, a Rho GTPase, under the control of a DC-specific CD11c-promoter. Transgenic mice (CD11c-N17Rac1) expressing dominant negative variants of Rac-1 in DC show a reduction in CD8+ CD11chi DC number and a severely reduced capacity for the uptake of apoptotic cells in the remaining CD8+ CD11chi DC population. Infection experiments have shown that CD11c-N17Rac1 mice were fully susceptible to prion disease after oral and intraperitoneal inoculation with the RML prion strain, with CD11c-N17Rac1 mice having somewhat longer incubation times than respective wildtype controls. Furthermore, infection experiments have shown that the susceptibility to oral prion infection in CD11c-N17Rac1 mice is independent of strain specificity, as CD11c-N17Rac1 mice were fully susceptible to oral infection with the ME7 prion strain. These results indicate that a severe impairment in CD8+ CD11chi DC number and function does not prevent scrapie pathogenesis after oral or intraperitoneal infection with prions. The fact that the CD11c-N17Rac1 transgenic mouse model showed a more pronounced effect on incubation time after intraperitoneal inoculation than after oral inoculation could indicate that oral and intraperitoneal scrapie infection differ in their lymphoreticular requirements. Detailed histological analyses are being performed to assess spleen structure in CD11c-N17Rac1 mice and to see if splenic PrPsc accumulation differs in amount and localisation between transgenic CD11c-N17Rac1 mice and respective controls.
AD Christian Hinske, Shneh Sethi, Armin Giese, Isabella Wagner, Jens Wagner, Sabine Ebner, Hans A. Kretzschmar, Center for Neuropathology and Prion Research, Ludwig-Maximilians Universität München,Germany; Kristen Kerksiek, Thomas Brocker, Institute for Immunology, Ludwig-Maximilians Universität München, Germany
SP englisch
PO Deutschland
OR Tagungsband