NR ATFQ
AU Barron,R.M.; Campbell,S.L.; King,D.; Chapman,K.; Manson,J.C.
TI Is PrPsc Associated with TSE Infectivity?
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Oral sessions ORAL-21
PT Konferenz-Vortrag
AB
The Prion hypothesis predicts that the aetiological agent of the Transmissible Spongiform Encephalopathy diseases is an abnormally folded isoform of a host glycoprotein, PrP. This abnormal proteinase K (PK) resistant isoform (PrPsc) is deposited in infected tissue, and co-purifies with infectivity. Definitive diagnosis of TSE disease can only be obtained by transmission studies to mice or other mammals. However these experiments are expensive and time consuming. Current diagnostic methods are therefore based on the detection of PK-resistant PrPsc in post mortem brain tissue, and its identification is taken as indicative of the presence of TSE infectivity.
The relationship between PrPsc and TSE infectivity is however still unclear. If PrPsc is not associated with infectivity, its reliability as a diagnostic marker in all cases of disease may be questionable. We have identified two mouse models of TSE disease in which high titres of infectivity are associated with low or undetectable levels of PrPsc in brain tissue, as measured by immunoblot and DELFIA. PrP in these mice appears to display the same detergent solubility and PK sensitivity as normal PrP (PrPc), despite the presence of high levels of the infectious agent. We aim to utilise these models to investigate the true nature of the TSE infectious agent, and identify other disease specific markers which may be useful in diagnosis.
AD R.M.Barron, S.L.Campbell, D.King, J.C.Manson, Institute for Animal Health, NPU, Edinburgh, UK; K.Chapman, Molecular Medicine Centre, WGH, Edinburgh, UK
SP englisch
PO Deutschland