Abnormal prion protein in genetically resistant sheep from a scrapie-infected flock.
The central molecular event in transmissible spongiform encephalopathies, such as scrapie in sheep, is the accumulation in tissues of an abnormal isoform of the cellular prion protein. A previous investigation of 26 sheep showed that the accumulation of PrP(res) in brain correlated more with the prnp genotype than with the severity of the clinical disease. Here, the ability of a sandwich ELISA to detect PrP(res) distribution in the brain was demonstrated. Immunohistochemistry also strongly supported the hypothesis that the dorsal motor nucleus of the vagus nerve is the possible entry site in the brain for the scrapie agent. Remarkably, three asymptomatic (or possibly asymptomatic for scrapie) sheep carrying an allele known to be associated with clinical scrapie resistance (ARR), which were negative for the detection of PrP(res) by Western blotting and immunohistochemistry, were positive for the presence of PrP(res) by ELISA, raising the possibility of carriers resistant to the disease and possibly contributing to the persistence of scrapie in certain flocks.
AFSSA Lyon, 31 avenue Tony Garnier, 69364 Lyon cedex 07, France.
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JY
Madec
CEA, Service de Pharmacologie et d'Immunologie, CEA/Saclay, France.
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S
Simon
AFSSA Lyon, 31 avenue Tony Garnier, 69364 Lyon cedex 07, France.
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Lezmi
AFSSA Lyon, 31 avenue Tony Garnier, 69364 Lyon cedex 07, France.
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Bencsik
CEA, Service de Pharmacologie et d'Immunologie, CEA/Saclay, France.
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J
Grassi
AFSSA Lyon, 31 avenue Tony Garnier, 69364 Lyon cedex 07, France.
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Baron
D000483:Alleles; D000818:Animals; D001921:Brain / Q000378:metabolism; D002353:Carrier State / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005838:Genotype; D007113:Immunity, Innate / Q000235:genetics; D018620:PrPSc Proteins / Q000032:analysis / Q000378:metabolism; D011328:Prions / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms / Q000032:analysis / Q000378:metabolism; D012608:Scrapie / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D012756:Sheep / Q000235:genetics*
D018620:PrPSc Proteins; D011328:Prions; D020033:Protein Isoforms