1. Goats naturally devoid of PrPC are resistant to scrapie
- Author
-
Michael A. Tranulis, Tram Thu Vuong, Øyvind Salvesen, Arild Espenes, Olivier Andreoletti, Cecilie Ersdal, Malin Rokseth Reiten, Ingrid Olsaker, Giulia Malachin, Linh T. Tran, Sylvie L. Benestad, Norwegian University of Life Sciences (NMBU), Dept Prod Anim Clin Sci, Norwegian School of Veterinary Science, Dept Basic Sci & Aquat Med, Norwegian Veterinary Institute [Oslo], Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and The research was supported by The Research Council of Norway (grant ID 227386/E40).
- Subjects
040301 veterinary sciences ,[SDV]Life Sciences [q-bio] ,animal diseases ,Central nervous system ,Scrapie ,Biology ,medicine.disease_cause ,Incubation period ,PRNP ,0403 veterinary science ,03 medical and health sciences ,mental disorders ,medicine ,Animals ,PrPC Proteins ,Gene ,030304 developmental biology ,Disease Resistance ,chemistry.chemical_classification ,0303 health sciences ,Mutation ,Goat Diseases ,lcsh:Veterinary medicine ,General Veterinary ,Goats ,food and beverages ,04 agricultural and veterinary sciences ,Virology ,3. Good health ,nervous system diseases ,Enzyme ,medicine.anatomical_structure ,chemistry ,Immunohistochemistry ,lcsh:SF600-1100 ,Female ,human activities ,Research Article - Abstract
Prion diseases are progressive and fatal, neurodegenerative disorders described in humans and animals. According to the “protein-only” hypothesis, the normal host-encoded prion protein (PrPC) is converted into a pathological and infectious form (PrPSc) in these diseases. Transgenic knockout models have shown that PrPC is a prerequisite for the development of prion disease. In Norwegian dairy goats, a mutation (Ter) in the prion protein gene (PRNP) effectively blocks PrPC synthesis. We inoculated 12 goats (4 PRNP+/+, 4 PRNP+/Ter, and 4 PRNPTer/Ter) intracerebrally with goat scrapie prions. The mean incubation time until clinical signs of prion disease was 601 days post-inoculation (dpi) in PRNP+/+ goats and 773 dpi in PRNP+/Ter goats. PrPSc and vacuolation were similarly distributed in the central nervous system (CNS) of both groups and observed in all brain regions and segments of the spinal cord. Generally, accumulation of PrPSc was limited in peripheral organs, but all PRNP+/+ goats and 1 of 4 PRNP+/Ter goats were positive in head lymph nodes. The four PRNPTer/Ter goats remained healthy, without clinical signs of prion disease, and were euthanized 1260 dpi. As expected, no accumulation of PrPSc was observed in the CNS or peripheral tissues of this group, as assessed by immunohistochemistry, enzyme immunoassay, and real-time quaking-induced conversion. Our study shows for the first time that animals devoid of PrPC due to a natural mutation do not propagate prions and are resistant to scrapie. Clinical onset of disease is delayed in heterozygous goats expressing about 50% of PrPC levels.
- Published
- 2020
- Full Text
- View/download PDF