NR AXVF
AU Ritchie,D.L.; Head,M.W.; Boyle,A.; Ironside,J.W.; Bruce,M.E.
TI Molecular and Biological Strain Typing of Sporadic and Variant Creutzfeldt-Jakob Disease
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Natural and Experimental Strains P02.18
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Background: The presence of distinct human prion strains has been inferred from the phenotypic heterogeneity observed in sporadic CJD. Classically, TSE strains are defined by their biological properties after transmission to inbred lines of mice, specifically by incubation period and pattern of vacuolar pathology in specified brain regions (the lesion profile). More recently, it has been proposed that PrPres may act as the surrogate marker for agent strain in what has been commonly referred to as 'molecular strain typing'.
Objectives: We aim to examine the relationship between PrPres type and agent strain by transmission of different subtypes of sporadic CJD, as classified according to PRNP codon 129 genotype and PrPres type, to wild-type mice and to compare these with transmission of variant CJD.
Materials and methods: Wild-type VM and RIII mice were experimentally challenged with brain homogenate from sporadic or variant CJD patients. At post-mortem, formalin fixed tissue was taken for pathological and immunohistochemical analysis and frozen CNS tissue taken for biochemical analysis.
Results: Preliminary results show the successful transmission of variant CJD and some subtypes of sporadic CJD to VM and RIII mice. Sporadic CJD transmission occurs only from cases containing at least one methionine at PRNP codon 129. Within the sporadic CJD cases that did transmit, transmission occurred from cases with type 1 and type 2
PrPres.
However, the lesion profiles from sporadic CJD transmissions show a similar pathology in all cases and in both mouse strains. In transmissions from sporadic and variant CJD showing positive pathology, Western blot analysis of PrPres in the CJD inoculum and the recipient mouse brain show conservation of PrPres type apart from the single successful sCJD MV2 transmission in which a PrPres type 1 was observed in the recipient mouse.
Conclusion: These transmission studies confirm the biochemical and biological differences between the agents responsible for sporadic CJD and variant CJD, but interestingly classical strain typing fails to confirm the differences in agent strain proposed to account for the pathological subtypes of sporadic CJD.
AD D. Ritchie, M.W. Head, J.W. Ironside, University of Edinburgh, National CJD Surveillance Unit, UK; A. Boyle, M.E. Bruce, Roslin Institute, Neuropathogenesis Unit, UK
SP englisch
PO Schottland