NR ATEY
AU Manson,J.C.
TI The role of PrP in TSE strains and the species barrier
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Oral sessions ORAL-03
PT Konferenz-Vortrag
AB PrP is central to TSE disease and has been hypothesised to be the infectious agent. Polymorphisms in the PrP gene are associated with different incubation times of disease following exposure to an infectious agent and mutations in the human PrP gene can apparently lead to spontaneous genetic disease. Strains of TSE agent are proposed to be generated and maintained through differences in glycosylation or conformation of PrP and the barrier to infection between species is thought to be due to the differences in the sequence of PrP between different species. To test these hypotheses, we have introduced specific modifications into the endogenous mouse Prnp gene by gene targeting. The mutated PrP gene is in the correct location under the control of the endogenous Prnp regulatory sequences and thus expressed in the same tissues and amounts as the wild type Prnp gene. By altering the murine PrP coding region to that of another species we have established that increasing overall identity between host and donor PrP can lead to either an increase or a decrease in incubation time of disease in a strain dependent manner. Moreover a point mutation in the N-terminus of the host PrP has produced dramatic changes in the susceptibility of the host to infection from different species. Mutations into the Prnp gene which alter the glycosylation of PrP have established a complex relationship between glycosylation of host PrP, incubation time of disease, vacuolar pathology and strain determination.
AD J.C.Manson, Institute for Animal Health, NPU, Ogston Building, West Mains Road, EH9 3JF Edinburgh, UK
SP englisch
PO Deutschland