NR AXRS
AU Rost,R.; Lutzny,G.; Maas,E.; Gädtke,L.; Geissen,M.; Groschup,M.H.; Onodera,T.; Schätzl,H.; Vorberg,I.
TI Ectopic Expression of Prion Protein Renders PrP Knock-out Cells Permissive to Scrapie
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Natural and Experimental Strains P02.04
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB Prion diseases are slow neurodegenerative diseases and include scrapie of sheep and goat, Creutzfeldt-Jakob disease and bovine spongiform encephalopathy. Expression of the cellular prion protein (PrPc) is crucial for susceptibility to prions, a fact that has formally been demonstrated using transgenic animals with an ablated prion protein gene. Ectopic expression of PrPc restores susceptibility to prion infection and transgenic mice that express heterologous PrP on a PrP knock out background have been used extensively to study the role of PrP alterations for prion transmission. In cell culture, heterologous PrP could only be studied on a PrP wild-type background, making it unclear whether wild-type or ectopic PrPsc catalyzed the conformational change of PrPc to its abnormal isoform. Here we report that prion protein knock-out cells can be rendered permissive to scrapie infection with different strains upon ectopic expression of PrP. Infection kinetics demonstrated that a 3 hour exposure to scrapie brain homogenate was sufficient for efficient infection. Interestingly, prion infectivity was also released into the cell culture supernatant. Due to the fact that prions propagated in this cell culture system are also infectious in vivo, their transmission to mice could potentially help to elucidate the role of PrP sequence alterations on incubation times and neuropathological changes.
AD G. Lutzny, E. Maas, L. Gädtke, H. Schätzl, I. Vorberg, Institute of Virology, Prion Research Group, Germany; M. Geissen, Institute of Neuropathology, Germany; M.H. Groschup, Friedrich-Löffler-Institut, Institute for Novel and Emerging Infectious Dis., Germany; T. Onodera, Department of Molecular Immunology, Graduate School of Agricultural and Life Sciences, Japan
SP englisch
PO Schottland