NR AWBE
AU Arsac,J.N.; Betemps,D.; Feraudet,C.; Debeurme,F.; Perdriau,M.; Benestad,S.L.; Grassi,J.; Baron,T.G.M.
TI Molecular signature of atypical scrapie as observed in field isolates and after transmission in an ovine transgenic mouse model (tgovPrP4)
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions PR-01
PT Konferenz-Poster
AB In this study we investigated a series of sheep and goats TSE isolates identified in France following active surveillance of scrapie between 2002 and 2004 which were identified as atypical cases of scrapie (Buschmamn et al., 2004). We performed a detailed analysis of PrPsc biochemical signature (WB electrophoretic mobility, epitope mapping and PrPsc deglycosylation pattern) and transmission results to transgenic mice over-expressing the ovine PrP A136 L141R154 Q171 allele (TgOvPrP4 mouse line) (Crozet et al., 2001). In all the field isolates we found an unique biochemical signature with five major bands including a characteristic band of low apparent molecular weight ( 10-11kDa). This unique pattern was shown to be undistinguishable from Norwegian Nor98 isolates and was fully conserved after transmission to ovine transgenic mice from a series of 11 different French isolates of different PrnP genotypes and species. Detailed analyses, in both small ruminants and ovine transgenic mice, strongly suggest that this unique pattern could originate from the presence of three different protease cleavage products, (i) a full length form of PrP, almost entirely protected against digestion by proteinase K, (ii) a 10-11kDa form cleaved in both N and C terminal ends of the protein (iii) and an 18kDa fragment probably Nterminally cleaved. Interestingly, in our ovine transgenic mouse model, we made the observation that PrPc levels detected in the blood at the time of intracerebral inoculation strongly determined the incubation period of the disease with atypical scrapie isolates. Mice with low levels of PrPc in the blood had very prolonged incubation periods. This was not observed with classical scrapie isolates. However PrPc blood levels did not influence the nature of clinical signs or PrPres Western blot pattern. These data have to be discussed with regard to other forms of prion diseases, including genetic (Gerstmann-Sträussler-Scheinker) and sporadic (CJD disease) forms in human. They raise essential questions regarding the aetiology of this recently described form of scrapie frequently observed throughout European countries.
AD J.-N. Arsac, D. Betemps, F. Debeurme, M. Perdriau, T. Baron: AFSSA-Lyon, Unité ATNC, 31 Avenue Tony Garnier, 69364 Lyon Cedex 07, France; C. Feraudet, J. Grassi: CEA, Service de Pharmacologie et d'Immunologie, CEA/Saclay, 91191 Gif sur Yvette cedex, France; S.L. Benestad: National Veterinary Institute, P.O.Box 8156 Dep., 0033 Oslo, Norway. E-mail: jn.arsac@lyon.afssa.fr
SP englisch
PO Italien