Bona fide atypical scrapie faithfully reproduced for the first time in a rodent model
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Author
Sánchez‑Martín, Manuel A.
Eraña, Hasier
Pérez Lázaro, Sonia
Pérez‑Castro, Miguel A.
Otero, Alicia
Charco, Jorge M.
Marín, Belén
López‑Moreno, Rafael
Díaz‑Domínguez, Carlos M.
Geijo, Mariví
Ordóñez, Montserrat
di Bari, Michele
Lorenzo, Nuria L.
Pirisinu, Laura
d’Agostino, Claudia
Torres, Juan María
Béringue, Vincent
Telling, Glenn
Badiola, Juan J.
Pumarola, Martí
Bolea, Rosa
Nonno, Romolo
Requena, Jesús R.
Castilla, Joaquín
Publication date
2022-12-13ISSN
2051-5960
Abstract
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.
Document Type
Article
Document version
Published version
Language
English
Subject (CDU)
619 - Veterinary science
Pages
22
Publisher
BMC
Is part of
Acta Neuropathologica Communications
Citation
Vidal, Enric, Manuel A. Sánchez-Martín, Hasier Eraña, Sonia Pérez Lázaro, Miguel A. Pérez-Castro, Alicia Otero, Jorge M. Charco, Belén Marín, Rafael López‑Moreno, Carlos M. Díaz‑Domínguez, Mariví Geijo, Montserrat Ordóñez, Guillermo Cantero, Michele di Bari, Nuria L. Lorenzo, Laura Pirisinu, Claudia d’Agostino, Juan María Torres, Vincent Béringue, Glenn Telling, Juan J. Badiola, Martí Pumarola, Rosa Bolea, Romolo Nonno, Jesús R. Requena and Joaquín Castilla. 2022. "Bona Fide Atypical Scrapie Faithfully Reproduced For The First Time In A Rodent Model". Acta Neuropathologica Communications 10 (1). doi:10.1186/s40478-022-01477-7.
Grant agreement number
MINECO/Programa Estatal de fomento de la investigación científica y técnica de excelencia/AGL2013-46756-P/ES/ESTUDIO DE MODELOS DE INFECTIVIDAD ESPONTANEA (Y SU POTENCIAL ZOONOTICO) EN ENFERMEDADES PRIONICAS EN ESPECIES DE INTERES GANADERO (OVINA Y BOVINA)/
MC/Programa Estatal para impulsar la investigación científico-técnica y su transferencia/PID2021-122201OB-C21/ES/ANALISIS DEL MALPLEGAMIENTO IN VITRO DE UNA DIVERSIDAD DE PROTEINAS DEL PRION PARA LA GENERACION DE NUEVAS ENTIDADES INFECCIOSAS Y DESARROLLO DE APROXIMACIONES TERAPEUTICAS/
MC/Programa Estatal de generación del conocimiento y fortalecimiento científico y tecnológico del sistema I+D+I y Programa Estatal de I+D+I orientada a los retos de la sociedad/PID2020-117465GB-I00/ES/ /
EC/INTERREG-POCTEFA/EFA-148-16/EU/ /REDPRION
FEDER/ / /EU/ /
Program
Sanitat Animal
This item appears in the following Collection(s)
- ARTICLES CIENTÍFICS [2555]
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Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/