Dogs are resistant to prion infection, due to the presence of aspartic or glutamic acid at position 163 of their prion protein

Enric Vidal, Natalia Fernández-Borges, Hasier Eraña, Beatriz Parra, Belén Pintado, Manuel A. Sánchez-Martín, Jorge M. Charco, Montserrat Ordóñez, Miguel A. Pérez-Castro, Martí Pumarola, Candace K. Mathiason, Tomás Mayoral, Joaquín Castilla*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

Abstract

Unlike other species, prion disease has never been described in dogs even though they were similarly exposed to the bovine spongiform encephalopathy (BSE) agent. This resistance prompted a thorough analysis of the canine PRNP gene and the presence of a negatively charged amino acid residue in position 163 was readily identified as potentially fundamental as it differed from all known susceptible species. In the present study, the first transgenic mouse model expressing dog prion protein (PrP) was generated and challenged intracerebrally with a panel of prion isolates, none of which could infect them. The brains of these mice were subjected to in vitro prion amplification and failed to find even minimal amounts of misfolded prions providing definitive experimental evidence that dogs are resistant to prion disease. Subsequently, a second transgenic model was generated in which aspartic acid in position 163 was substituted for asparagine (the most common in prion susceptible species) resulting in susceptibility to BSE-derived isolates. These findings strongly support the hypothesis that the amino acid residue at position 163 of canine cellular prion protein (PrPC) is a major determinant of the exceptional resistance of the canidae family to prion infection and establish this as a promising therapeutic target for prion diseases.

Original languageAmerican English
Pages (from-to)3969-3982
Number of pages14
JournalFASEB journal
Volume34
Issue number3
DOIs
Publication statusPublished - 1 Mar 2020

Keywords

  • canids
  • canine
  • dog
  • interspecies transmission
  • prion infection
  • prion susceptibility
  • scrapie
  • transgenic mouse models
  • transmissible spongiform encephalopathy
  • transmission barrier

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