Bona fide atypical scrapie faithfully reproduced for the first time in a rodent model.

Autor: Vidal E; Unitat Mixta d'Investigació IRTA-UAB en Sanitat Animal, Centre de Recerca en Sanitat Animal (CReSA), Campus de la Universitat Autònoma de Barcelona (UAB), Bellaterra, Catalonia, Spain.; IRTA Programa de Sanitat Animal, Centre de Recerca en Sanitat Animal (CReSA), Campus de la Universitat Autònoma de Barcelona (UAB), Bellaterra, Catalonia, Spain., Sánchez-Martín MA; Transgenic Facility. Department of Medicine, University of Salamanca, 37007, Salamanca, Spain., Eraña H; Centro de Investigación Cooperativa en Biociencias (CIC BioGUNE), Laboratorio de Investigación de Priones, Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain.; ATLAS Molecular Pharma S. L., Derio, Bizkaia, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain., Lázaro SP; Centro de Encefalopatías y Enfermedades Transmisibles Emergentes, Facultad de Veterinaria, Universidad de Zaragoza-IA2, Zaragoza, Spain., Pérez-Castro MA; Centro de Investigación Cooperativa en Biociencias (CIC BioGUNE), Laboratorio de Investigación de Priones, Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain., Otero A; Centro de Encefalopatías y Enfermedades Transmisibles Emergentes, Facultad de Veterinaria, Universidad de Zaragoza-IA2, Zaragoza, Spain., Charco JM; Centro de Investigación Cooperativa en Biociencias (CIC BioGUNE), Laboratorio de Investigación de Priones, Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain.; ATLAS Molecular Pharma S. L., Derio, Bizkaia, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain., Marín B; Centro de Encefalopatías y Enfermedades Transmisibles Emergentes, Facultad de Veterinaria, Universidad de Zaragoza-IA2, Zaragoza, Spain., López-Moreno R; Centro de Investigación Cooperativa en Biociencias (CIC BioGUNE), Laboratorio de Investigación de Priones, Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain., Díaz-Domínguez CM; Centro de Investigación Cooperativa en Biociencias (CIC BioGUNE), Laboratorio de Investigación de Priones, Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain., Geijo M; Animal Health Department, NEIKER-Basque Institute for Agricultural Research and Development, Basque Research and Technology Alliance (BRTA), Derio, Spain., Ordóñez M; Unitat Mixta d'Investigació IRTA-UAB en Sanitat Animal, Centre de Recerca en Sanitat Animal (CReSA), Campus de la Universitat Autònoma de Barcelona (UAB), Bellaterra, Catalonia, Spain.; IRTA Programa de Sanitat Animal, Centre de Recerca en Sanitat Animal (CReSA), Campus de la Universitat Autònoma de Barcelona (UAB), Bellaterra, Catalonia, Spain., Cantero G; Unitat Mixta d'Investigació IRTA-UAB en Sanitat Animal, Centre de Recerca en Sanitat Animal (CReSA), Campus de la Universitat Autònoma de Barcelona (UAB), Bellaterra, Catalonia, Spain.; IRTA Programa de Sanitat Animal, Centre de Recerca en Sanitat Animal (CReSA), Campus de la Universitat Autònoma de Barcelona (UAB), Bellaterra, Catalonia, Spain., di Bari M; Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore Di Sanità, 00161, Rome, Italy., Lorenzo NL; CIMUS Biomedical Research Institute, University of Santiago de Compostela-IDIS, Santiago, Spain., Pirisinu L; Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore Di Sanità, 00161, Rome, Italy., d'Agostino C; Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore Di Sanità, 00161, Rome, Italy., Torres JM; Centro de Investigación en Sanidad Animal (CISA), Centro Superior de Investigaciones Científicas (CSIC) Valdeolmos, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), 28130, Madrid, Spain., Béringue V; Molecular Virology and Immunology, Institut National de La Recherche Agronomique (INRA), Université Paris-Saclay, Jouy-en-Josas, France., Telling G; Prion Research Center (PRC) and the Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO, USA., Badiola JJ; Centro de Encefalopatías y Enfermedades Transmisibles Emergentes, Facultad de Veterinaria, Universidad de Zaragoza-IA2, Zaragoza, Spain., Pumarola M; Departament de Medicina i Cirurgia Animals, Facultat de Veterinària, Campus de UAB, Bellaterra, 08193, Barcelona, Catalonia, Spain., Bolea R; Centro de Encefalopatías y Enfermedades Transmisibles Emergentes, Facultad de Veterinaria, Universidad de Zaragoza-IA2, Zaragoza, Spain., Nonno R; Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore Di Sanità, 00161, Rome, Italy., Requena JR; CIMUS Biomedical Research Institute, University of Santiago de Compostela-IDIS, Santiago, Spain., Castilla J; Centro de Investigación Cooperativa en Biociencias (CIC BioGUNE), Laboratorio de Investigación de Priones, Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain. jcastilla@cicbiogune.es.; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain. jcastilla@cicbiogune.es.; IKERBASQUE, Basque Foundation for Science, Bilbao, Bizkaia, Spain. jcastilla@cicbiogune.es.
Jazyk: angličtina
Zdroj: Acta neuropathologica communications [Acta Neuropathol Commun] 2022 Dec 13; Vol. 10 (1), pp. 179. Date of Electronic Publication: 2022 Dec 13.
DOI: 10.1186/s40478-022-01477-7
Abstrakt: 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 PrP C 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 PrP res 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 PrP C ), Tg338 (ovine VRQ PrP C ), Tg501 (ovine ARQ PrP C ), Tg340 (human M129 PrP C ), Tg361 (human V129 PrP C ), TgVole (bank vole I109 PrP C ), bank vole (I109I PrP C ), 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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