NR AWPJ
AU Tuzi,N.L.; Cancellotti,E.; Baybutt,H.N.; Aitchison,L.; Bradford,B.; Piccardo,P.; Barron,R.M.; Hart,P.; Plinston,C.; Manson,J.C.
TI Host PrP glycosylation influences the outcome of transmissible spongiform encephalopathy infection
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 PA-57
PT Konferenz-Poster
AB PrP possessed two potential sites for N-linked glycosylation which together with the complexity of the added sugars allows for the generation of a very large number of different glycosylated forms of PrP. Numerous prion or transmissible spongiform encephalopathy (TSE) strains exist, but to date the underlying nature of these strains that gives rise to their different properties remains elusive. However, it has been proposed that the variation in PrP molecules arising from differential glycosylation may account for, or contribute to, the many TSE strains and their characteristics. Therefore to investigate this possibility we have generated three lines of gene targeted transgenic mice with mutations at the first (G1), second (G2) or both (G3) glycosylation sites thus preventing the addition of N-linked glycans at these sites. By using the gene targeting approach we can ensure the altered PrP gene is in the endogenous position in the genome and is thus under its normal control elements thereby eliminating the complication of overexpression and/or ectopic expression. We have established that despite differences in cellular location, mono and un-glycosylated PrP can support both clinical and pathological disease, albeit with varying degrees of susceptibility, following TSE challenge. Moreover different TSE agents have dramatically different requirements for glycosylation of host PrP. We have also demonstrated that TSE strain characteristics can be modified when passaged through hosts with altered PrP glycosylation. Therefore, we consider glycoform analysis should be used with caution as a means of defining the TSE strain infecting the host.
AD N.L. Tuzi, E. Cancellotti, H. Baybutt, L. Aitchison, B. Bradford, R.M. Barron, P. Hart, C. Plinston, J. Manson: Institute for Animal Health, Neuropathogenesis Unit, Edinburgh, UK; P. Piccardo: Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD 20852, USA. E-mail: nadia.tuzi@bbsrc.ac.uk
SP englisch
PO Italien