title: Early detection of PrPres in BSE-infected bovine PrP transgenic mice.
abstract: Transgenic mouse lines expressing different levels of the bovine prion protein gene (boPrP(C)) were generated. Upon infection with BSE prions, all transgenic lines tested exhibited characteristics of the bovine disease. Typical CNS spongiform degeneration was observed by histopathology and presence of PrP(res) could be detected both by Western blot and immunohistochemistry (IHC) assays, confirming for this model the absence of an interspecies barrier to BSE infection. Differences in incubation times post-inoculation depend upon the expression level of boPrP(C) and the amount of prions in the inoculum. In the absence of clinical signs, pathognomonic markers of disease could be detected as early as 150 or 196 days post-inoculation by IHC and Western blot analysis, respectively. This result indicates that prion infectivity in experimental mouse bioassays can be measured earlier by assessing immunologically the presence of PrP(res) in brains from inoculated animals. Although these transgenic mice were also susceptible to sheep scrapie prion infection, the extent of incubation times was considerably longer and PrP(res) was detected in only 70 % of inoculated mice. Interestingly, transgenic mice-propagated sheep scrapie prions displayed distinct biochemical properties when compared to both the original sheep scrapie and transgenic mouse-propagated BSE inoculum.
authors.affiliation: Centro de Investigación en Sanidad Animal, INIA, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Castilla
authors.forename: A
authors.initials: A
authors.lastname: Gutiérrez Adán
authors.forename: A
authors.initials: A
authors.lastname: Brun
authors.forename: B
authors.initials: B
authors.lastname: Pintado
authors.forename: M A
authors.initials: MA
authors.lastname: Ramírez
authors.forename: B
authors.initials: B
authors.lastname: Parra
authors.forename: D
authors.initials: D
authors.lastname: Doyle
authors.forename: M
authors.initials: M
authors.lastname: Rogers
authors.forename: F J
authors.initials: FJ
authors.lastname: Salguero
authors.forename: C
authors.initials: C
authors.lastname: Sánchez
authors.forename: J M
authors.initials: JM
authors.lastname: Sánchez-Vizcaíno
authors.forename: J M
authors.initials: JM
authors.lastname: Torres
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002417:Cattle; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D016643:Encephalopathy, Bovine Spongiform / Q000378:metabolism* / Q000473:pathology; D019286:Endopeptidase K; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000378:metabolism; D018621:PrPC Proteins / Q000032:analysis / Q000235:genetics; D011328:Prions / Q000032:analysis* / Q000378:metabolism; D012608:Scrapie / Q000378:metabolism / Q000473:pathology; D013045:Species Specificity; D013997:Time Factors
chemical_list: D009419:Nerve Tissue Proteins; D018621:PrPC Proteins; D011328:Prions; D019286:Endopeptidase K