JOURNAL ARTICLE

Neuronal accumulation of abnormal prion protein in sheep carrying a scrapie-resistant genotype (PrPARR/ARR)

Anne Buschmann, Gesine Lühken, Julia Schultz, G Erhardt, Martin H Groschup
Journal of General Virology 2004, 85: 2727-33
15302966
The susceptibility of sheep to scrapie infection is influenced by prion gene alleles, which are modulated by polymorphic variations corresponding to amino acid positions 136, 154 and 173 of the prion protein (PrP). As no unquestioned report of a diseased sheep carrying homozygous alleles encoding alanine, arginine and arginine (PrPARR) at these sites has been published to date, sheep of this genotype are believed to be scrapie resistant. After the introduction of large-scale rapid testing for scrapie, a number of so-called 'atypical' scrapie cases have been found in Germany and elsewhere. Among those cases were two supposedly scrapie-resistant sheep. Brain samples from these animals tested positive for abnormal PrP (PrPSc) in one of four rapid tests available. Moreover, scrapie-associated fibril (SAF)-immunoblotting and immunohistochemistry, which are the generally accepted diagnostic techniques for scrapie, revealed prominent PrPSc deposition in the cerebellum. SAF immunoblotting also revealed PrPSc deposition in the obex, frontal cortex and brainstem. Transmission experiments to investigate the infectivity of scrapie propagated from these sheep have been initiated.

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