Transgenic Mouse Bioassay: Evidence That Rabbits Are Susceptible to a Variety of Prion Isolates

PLoS Pathogens

Hasier Eraña¹  Natalia Fernández-Borges¹  Joaquín Castilla¹  Belén Pintado²  Dolors Fondevila³  Martí Pumarola³  Mercedes Márquez³  Olivier Andreoletti⁴  Enric Vidal⁵  Montserrat Ordóñez⁵  Mark P. Dagleish⁶  Francesca Chianini⁶  Manuel A. Sánchez-Martín⁷ 

[1] CIC bioGUNE, Parque tecnológico de Bizkaia, Derio, Bizkaia, Spain;Centro Nacional de Biotecnología (CNB), Campus de Cantoblanco, Cantoblanco, Madrid, Spain;Department of Animal Medicine and Surgery, Veterinary faculty, Universitat Autònoma de Barcelona (UAB), Bellaterra (Cerdanyola del Vallès), Barcelona, Catalonia, Spain;Ecole Nationale du Veterinaire, Service de Pathologie du Bétail, Toulouse, France;IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Autònoma de Barcelona, Bellaterra, Spain;Moredun Research Institute, Pentlands Science Park, Bush Loan, Penicuik, Near Edinburgh, Scotland, United Kingdom;Unidad de Generación de OMGs, S.E.A. Department of Medicine, University of Salamanca, Salamanca, Spain

关键词: Rabbits;    Animal prion diseases;    Mouse models;    Scrapie;    Cattle;    Sheep;    Chronic wasting disease;    Medulla oblongata;   

DOI  :  10.1371/journal.ppat.1004977

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Interspecies transmission of prions is a well-established phenomenon, both experimentally and under field conditions. Upon passage through new hosts, prion strains have proven their capacity to change their properties and this is a source of strain diversity which needs to be considered when assessing the potential risks associated with consumption of prion contaminated protein sources. Rabbits were considered for decades to be a prion resistant species until proven otherwise recently. To determine the extent of rabbit susceptibility to prions and to assess the effects of passage of different prion strains through this species a transgenic mouse model overexpressing rabbit PrPC was developed (TgRab). Intracerebral challenges with prion strains originating from a variety of species including field isolates (ovine SSBP/1 scrapie, Nor98- scrapie; cattle BSE, BSE-L and cervid CWD), experimental murine strains (ME7 and RML) and experimentally obtained ruminant (sheepBSE) and rabbit (de novo NZW) strains were performed. On first passage TgRab were susceptible to the majority of prions (Cattle BSE, SheepBSE, BSE-L, de novo NZW, ME7 and RML) tested with the exception of SSBP/1 scrapie, CWD and Nor98 scrapie. Furthermore, TgRab were capable of propagating strain-specific features such as differences in incubation periods, histological brain lesions, abnormal prion (PrPd) deposition profiles and proteinase-K (PK) resistant western blotting band patterns. Our results confirm previous studies proving that rabbits are not resistant to prion infection and show for the first time that rabbits are susceptible to PrPd originating in a number of other species. This should be taken into account when choosing protein sources to feed rabbits.

【 授权许可】

CC BY