Molecular behaviors of "CH1641-like" sheep scrapie isolates in ovine transgenic mice (TgOvPrP4).
Molecular analyses of the protease-resistant prion protein (PrP(res)) from a few natural scrapie isolates showed by Western blotting some partial similarities with those observed in experimental ovine bovine spongiform encephalopathy (BSE). They showed a low apparent molecular mass of unglycosylated PrP(res), although diglycosylated PrP(res) was less abundant than in ovine BSE. The prototype of such cases is the CH1641 experimental scrapie isolate. We analyzed PrP(res) molecular features from three French natural "CH1641-like" isolates, in comparison with CH1641 and BSE, after transmission of the disease in ovine transgenic mice (TgOvPrP4). One of these isolates (TR316211) behaved like the CH1641 isolate, with PrP(res) features in mice similar to those in the sheep brain. From two other isolates (O100 and O104), two distinct PrP(res) phenotypes were identified in mouse brains, with either high (h-type) or low (l-type) apparent molecular masses of unglycosylated PrP(res), the latter being similar to that observed with CH1641, TR316211, or BSE. Both phenotypes could be found in variable proportions in the brains of the individual mice. In contrast with BSE, l-type PrP(res) from "CH1641-like" isolates showed lower levels of diglycosylated PrP(res). From one of these cases (O104), a second passage in mice was performed for two mice with distinct PrP(res) profiles. This showed a partial selection of the l-type phenotype in mice infected with a mouse brain with predominant l-type PrP(res), and it was accompanied by a significant increase in the proportions of the diglycosylated band. These results are discussed in relation to the diversity of scrapie and BSE strains.
Baron
Thierry
T
Agence Française de Sécurité Sanitaire des Aliments-Lyon, Unité ATNC, Lyon, France. t.baron@lyon.afssa.fr
Biacabe
Anne-Gaëlle
AG
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002417:Cattle; D016643:Encephalopathy, Bovine Spongiform / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006031:Glycosylation; D051379:Mice; D008822:Mice, Transgenic; D018620:PrPSc Proteins / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D011499:Protein Processing, Post-Translational; D012608:Scrapie / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012756:Sheep
D018620:PrPSc Proteins