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

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.

• Authors: 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
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 34 Issue 3 Pg. 3969-3982 (03 2020) ISSN: 1530-6860 [Electronic] United States
• PMID: 31944411 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 Federation of American Societies for Experimental Biology.

Chemical References

• Prions
• Aspartic Acid
• Glutamic Acid
• Plasma Membrane Calcium-Transporting ATPases

Topics

• Animals
• Aspartic Acid (chemistry)
• Biological Assay
• Brain (pathology)
• Dogs
• Glutamic Acid (chemistry)
• Mice
• Plasma Membrane Calcium-Transporting ATPases (metabolism)
• Prions (chemistry, pathogenicity)