NR AXXZ
AU Tuzi,N.L.; Cancellotti,E.; Baybutt,H.; Blackford,L.; Bradford,B.; Piccardo,P.; Plinston,C.; Hart,P.; Barron,R.M.; Manson,J.C.
TI Host PrP Glycosylation; A Major Factor Determining the Outcome of Transmissible Spongiform Encephalopathy Infection
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Oral Abstracts FC3.3
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Vortrag
AB Expression of the PrP protein is essential for transmissible spongiform encephalopathy (TSE) or prion diseases to occur, but the underlying mechanism of infection remains unresolved. PrP is differentially glycosylated giving rise to di-, mono- and unglycosylated species but the significance of this variation in glycosylation is unknown. To address the hypothesis that glycosylation of host PrP is a major factor influencing TSE infection, we have inoculated our gene-targeted transgenic mice which possess restricted N-linked glycosylation of PrP with three TSE strains. We have demonstrated that glycosylation is not a prerequisite for TSE disease since we found that mice expressing only un-glycosylated PrP can sustain a TSE infection. Moreover we have shown that brain material from TSE infected mice possessing only un-glycosylated PrPsc is capable of transmitting infection to wild type mice, thus demonstrating for the first time that glycosylation of PrPsc is not necessary to allow transmission of TSE infectivity to a new host. The requirement of each PrP glycosylation site has been dissected further and has revealed that different TSE strains have dramatically different requirements for each of the glycosylation sites of host PrP and moreover we show that the host PrP has a major role in determining the glycosylation state of de novo generated PrPsc.
AD N.L. Tuzi, E. Cancellotti, H. Baybutt, L. Blackford, B. Bradford, C. Plinston, P. Hart, R.M. Barron, J.C. Manson, Neuropathogenesis Unit, Roslin Institute, UK; P. Piccardo, Centre for Biologics Evaluation and Research, Food and Drug Administration, USA
SP englisch
PO Schottland