Variability of pathological phenotypes within classical sheep scrapie cases has been reported for some time, but in many instances it has been attributed to differences in the genotype of the host. To address this issue we have examined by immunohistochemistry (IHC) and Western blotting (WB) for the disease-associated form of the prion protein (PrP), the brains of 23 sheep from five European countries, all of which were of the same ARQ/ARQ genotype. As a result of IHC examinations, sheep were distributed into five groups with different phenotypes and the groups were the same regardless of the scoring method used, ‘long’ or ‘short’ PrP profiling. The groups made did not respond to the geographical origin of the cases and did not correlate with the vacuolar lesion profiles, which showed a high individual variability. Discriminatory IHC and WB methods coincided to detect a ‘CH1641-like’ case but otherwise correlated poorly in the classification of disease phenotypes. No other polymorphisms of the gene were found that could account for the pathological differences, except perhaps for a sheep from Spain with a mutation at codon 103 and a unique pathological phenotype. Preliminary evidence indicates that those different IHC phenotypes correlate with distinct biological properties on bioassay, suggesting that they are indicative of strain diversity. We therefore conclude that natural scrapie strains exist and that they can be revealed by detailed pathological examinations, which can be harmonized between laboratories to produce comparable results.


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vol. , part 10, pp. 2630 - 2641

Short PrP profiles

Vacuolar lesion profiles

Summary of the correlation analyses of the vacuolar lesion profiles

Glycoprofile results and statistical analysis

Dendrogram for cluster analysis of short PrP profiles [Single PDF file](23 KB)

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