NR AXJB
AU Beck,K.; Sallis,R.; Simonini,S.; Spiropoulos,J.
TI Primary Isolation of the Scrapie Agent in RIII Mice: Identification of Sheep PrP Genotype-associated Profiles
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Natural and Experimental Strains P02.20
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Background: Lesion profile and incubation period analysis are effective mouse bioassay parameters for transmissible spongiform encephalopathy (TSE) strain analysis. Using these methods, RIII (Prnpa) mice have proven useful in distinguishing BSE from scrapie at primary isolation: BSE presents a reproducible lesion profile with peaks at brain areas 1, 4 and 7 (dorsal medulla, hypothalamus and septal nuclei), while classical scrapie lesion profiles are believed to be more variable.
Aim: The aim of this study was to analyse a large number of scrapie isolates in RIII mice and explore trends in the resulting lesion profiles and incubation periods at primary isolation.
Methods: 62 positive scrapie field cases were collected from individual farms. A 10 % obex homogenate was inoculated into RIII mice (20 mice per inoculum). Post mortem TSE diagnosis was confirmed histopathologically on H&E sections. Lesion profiles and incubation periods were assessed using standard methodology (Fraser and Dickinson, 1968).
Results: 31 inocula with 5 or more clinically and H&E positive mice were profiled. Profiles presented as 3 distinct subgroups. One subgroup comprising of 10 inocula showed consistent peaks at brain areas 1, 4 and 7. All inocula for this subgroup were derived from sheep of genotype ARQ/ARQ. The incubation period of disease in these mice was lower than other groups. Whilst this profile exhibits similarities to BSE in RIII mice at primary isolation, the profile described here was different in some respects, for example profiles were higher and a different shape. Also additional histopathology was not consistent with BSE. A second subgroup of 5 inocula gave an alternative 1-4-7 profile and derived from ARQ or VRQ homozygotes. A third non 1-4-7 profile was associated with the V allele in 13 of 16 inocula.
Conclusion: Results demonstrate that in RIII mice discrete classical scrapie profiles can be distinguished on primary isolation in contrast to previous belief. It appears that these profiles are associated with the PrP genotype of the sheep donor. Of particular interest is the ARQ/ARQ-associated 1-4-7 profile, where caution should be taken to distinguish this profile from BSE. Further studies are required to assess the stability of this profile on sub-passage.
AD K. Beck, R. Sallis, S. Simonini, J. Spiropoulos, Veterinary Laboratories Agency, UK
SP englisch
PO Schottland