NR AOZY
AU Tuzi,N.L.; Baybutt,H.N.; Aitchison,L.; Bradford,B.; Manson,J.C.
TI Investigation of the role of N-linked glycosylation of PrP in TSE disease using gene targeted transgenic mouse models
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-12
PT Konferenz-Poster
AB
Although the nature of the infectious agent in TSE diseases has yet to be identified, the prion hypothesis proposes that an altered form of the normal cellular protein, PrP, is responsible for propagating the disease. To explain the different strains of TSE identified, each with their own set of unique characteristics, it is proposed that a structural or post-translational modifications of PrP could give rise to the numerous TSE strains observed. One such post-translational modification is glycosylation. The PrP protein possesses two potential sites for N-linked glycosylation at positions 180 and 196 in murine PrP, where each site alone, both sites or neither sites can be occupied with sugars. Different regions of the uninfected mouse brain have been shown to express different glycoforms of PrP, and different strains of TSEs can possess different glycoforms of PrP. It is possible that the different strains of TSEs target specific regions of the brain due to the glycoform of the host PrP in that region.
Therefore to investigate the role of glycosylation of PrP in the targeting of TSE agents and in the maintenance of TSE strain characteristics, we have generated three lines of transgenic mice by gene targeting the endogenous murine Prnp gene. Mice possessing mutations at the first (G1), second (G2) or both (G3) glycosylation sites have now been produced. G2 mice have been infected with two strains of TSE agent via two routes. This will allow us to assess the role of glycosylation of PrP on strain targeting. Experiments on the sub-passage of brain material from TSE infected G2 mice are now nearing completion and will allow us to determine the effect of altering glycosylation of PrP on strain characteristics. Results from these studies will be presented.
AD Nadia L. Tuzi, Herbert Baybutt, Lorraine Aitchison, Barry Bradford, Jean C. Manson, Neuropathogenesis Unit, Institute for Animal Health, Edinburgh
SP englisch
PO Deutschland