Goats naturally devoid of PrP C are resistant to scrapie
In: ISSN: 0928-4249, 2020
Online
academicJournal
Zugriff:
International audience ; 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 (PrP C) is converted into a pathological and infectious form (PrP Sc) in these diseases. Transgenic knockout models have shown that PrP C is a prerequisite for the development of prion disease. In Norwegian dairy goats, a mutation (Ter) in the prion protein gene (PRNP) effectively blocks PrP C 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 PrP Sc 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 PrP Sc 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 PrP C 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 PrP C levels.
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Goats naturally devoid of PrP C are resistant to scrapie
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Autor/in / Beteiligte Person: | Salvesen, Øyvind ; Espenes, Arild ; Reiten, Malin R. ; Vuong, Tram T. ; Malachin, Giulia ; Tran, Linh ; Andréoletti, Olivier ; Olsaker, Ingrid ; Benestad, Sylvie L. ; Tranulis, Michael A. ; Ersdal, Cecilie ; 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 de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) ; The research was supported by The Research Council of Norway (grant ID 227386/E40). |
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Zeitschrift: | ISSN: 0928-4249, 2020 |
Veröffentlichung: | HAL CCSD ; BioMed Central, 2020 |
Medientyp: | academicJournal |
DOI: | 10.1186/s13567-019-0731-2 |
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