NR AWQP
AU Wiseman,F.; Cancellotti,E.; Castilla,J.; Tuzi,N.L.; Baybutt,H.N.; Aitchison,L.; Ironside,J.; Soto,C.; Manson,J.
TI Glycosylation of PrP and the transmissible spongiform encephalopathies species barrier
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-59
PT Konferenz-Poster
AB Cross species transmission of transmissible spongiform encephalopathies (TSE) to the human population is of major public health importance. The molecular factors governing the spread of TSE between host species are not fully understood; although host encoded PrP is thought to be central. PrP is variably glycosylated at two sites in vivo (N180 and N196 in mice). These N-glycans may greatly influence TSE transmission between species. To address this issue, we have transmitted human and hamster TSE strains to PrP glycosylation deficient transgenic mice, produced by gene targeting (G1 T180; G2 T196; G3 T180 and T196). These mice have an altered pattern of glycosylation of PrP but do not develop spontaneous disease. Here we present data showing a difference in the incubation period and disease incidence between the glycosylation deficient transgenics and control mice; demonstrating that PrP N-glycans do have a species barrier role. However, the nature of this role is dependent upon TSE strain and the site of host PrP N-glycan attachment. To further understand the relationship between PrP glycosylation state and cross species TSE susceptibility we have undertaken in vitro conversions to examine the underlying causes of the observed alteration of disease incidence and incubation period.
AD F. Wiseman, E. Cancellotti, N.L. Tuzi, H. Baybutt, L. Aitchison, J. Manson: Neuropathogenesis Unit, Institute for Animal Health, Edinburgh, UK; J. Castilla, C. Soto: Protein Misfolding Diseases Laboratory, University of Texas Medical Branch, Galveston, USA; J. Ironside: CJD Surveillance Unit, Western General Hospital, Edinburgh, UK
SP englisch
PO Italien