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| Pàgina inicial > Articles > Articles publicats > Bona fide atypical scrapie faithfully reproduced for the first time in a rodent model |
(Unitat mixta d'investigació IRTA-UAB en Sanitat Animal. Centre de Recerca en Sanitat Animal) (Instituto de Salud Carlos III. Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC)) (Basque Centre for Climate Change (Bilbao)) (Universidad de Zaragoza. Centro de Encefalopatías y Enfermedades Transmisibles Emergentes) (Centro de Investigación Biomédica en Red de Enfermedades Infecciosas) (Basque Centre for Climate Change (Bilbao)) (Institut de Recerca i Tecnologia Agroalimentàries. Centre de Recerca en Sanitat Animal) (Universitat Autònoma de Barcelona. Departament de Medicina i Cirurgia Animals) (Istituto Superiore Di Sanità. Department of Food Safety, Nutrition and Veterinary Public Health) (IKERBASQUE. Basque Foundation for Science)
| Data: | 2022 |
| Resum: | Atypical Scrapie, which is not linked to epidemics, is assumed to be an idiopathic spontaneous prion disease in small ruminants. Therefore, its occurrence is unlikely to be controlled through selective breeding or other strategies as it is done for classical scrapie outbreaks. Its spontaneous nature and its sporadic incidence worldwide is reminiscent of the incidence of idiopathic spontaneous prion diseases in humans, which account for more than 85% of the cases in humans. Hence, developing animal models that consistently reproduce this phenomenon of spontaneous PrP misfolding, is of importance to study the pathobiology of idiopathic spontaneous prion disorders. Transgenic mice overexpressing sheep PrPC with I112 polymorphism (TgShI112, 1-2 × PrP levels compared to sheep brain) manifest clinical signs of a spongiform encephalopathy spontaneously as early as 380 days of age. The brains of these animals show the neuropathological hallmarks of prion disease and biochemical analyses of the misfolded prion protein show a ladder-like PrPres pattern with a predominant 7-10 kDa band. Brain homogenates from spontaneously diseased transgenic mice were inoculated in several models to assess their transmissibility and characterize the prion strain generated: TgShI112 (ovine I112 ARQ PrPC), Tg338 (ovine VRQ PrPC), Tg501 (ovine ARQ PrPC), Tg340 (human M129 PrPC), Tg361 (human V129 PrPC), TgVole (bank vole I109 PrPC), bank vole (I109I PrPC), and sheep (AHQ/ARR and AHQ/AHQ churra-tensina breeds). Our analysis of the results of these bioassays concludes that the strain generated in this model is indistinguishable to that causing atypical scrapie (Nor98). Thus, we present the first faithful model for a bona fide, transmissible, ovine, atypical scrapie prion disease. |
| Ajuts: | Fundació la Marató de TV3 ATYPRION 201821-30-31-32 Ministerio de Ciencia, Innovación y Universidades AGL 2013-46756-P Ministerio de Ciencia, Innovación y Universidades PID2021-122201OB-C21 Ministerio de Ciencia e Innovación PID2020-117465GB-I00 |
| Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Matèria: | Atypical ; Scrapie ; Spontaneous ; Prion disease ; Isoleucine |
| Publicat a: | Acta neuropathologica communications, Vol. 10 (december 2022) , ISSN 2051-5960 |
