NR ATHF
AU Cancellotti,E.; Wiseman,F.; Tuzi,N.L.; Baybutt,H.N.; Aitchison,L.; Monaghan,P.; Simpson,J.; Manson,J.C.
TI Analysis of the role of glycosylation in PrP cell biology and TSE infection using gene-targeted murin models
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Cell Biology of PrPc and PrPsc CELL-11
PT Konferenz-Poster
AB N-linked glycans have been shown to have an important role in the cell biology of a variety of cell surface glycoproteins including PrP protein. It has been suggested that glycosylation of PrP can influence the susceptibility to transmissible spongiform encephalopathy (TSE) and determine the characteristics of the many different strains observed in this particular type of disease. To understand the role of carbohydrates in influencing the PrP cell biology and in modulating the TSE infectious process, we have produced and analyzed gene targeted murine models expressing altered glycosylated PrP. Transgenic mice carrying the PrP substitution threonine for asparagine180 (G1) or threonine for asparagine196 (G2) or both mutations combined (G3), which eliminate the first, second and both glycosylation sites respectively, have been generated by double replacement gene targeting. An in vivo analysis of altered PrP has been carried out in transgenic mice brains and our data show that the lack of glycans does not influence PrP maturation and stability. The presence of one chain of sugar is sufficient for the trafficking to cell membrane while the un-glycosylated PrP localization is mainly intracellular, however this altered cellular localization of PrP does not led to any overt phenotype in the G3 transgenic mice. Most importantly, we found that un-glycosylated PrP in vivo does not acquire the characteristics of the aberrant pathogenic form (PrPsc) as was previously reported using in vitro models. The data presented here together with infectivity studies carried out in these transgenics mice are important for understanding the role of carbohydrates in influencing the infectious process and the TSE strains properties.
AD Enrico Cancellotti, Frances Wiseman, Nadia L. Tuzi, Herbert Baybutt, Lorraine Aitchison1, Jean C. Manson, Neuropathogenesis Unit, Institute for Animal Health, Edinburgh UK; Paul Monaghan, Jennifer Simpson, Institute for Animal Health, Pirbright UK
SP englisch
PO Deutschland