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Related Experiment Video

Updated: Feb 15, 2026

Assessing Transmissible Spongiform Encephalopathy Species Barriers with an In Vitro Prion Protein Conversion Assay

Assessing Transmissible Spongiform Encephalopathy Species Barriers with an In Vitro Prion Protein Conversion Assay

Published on: March 10, 2015

Behind the potential evolution towards prion resistant species.

Natalia Fernández-Borges¹, Hasier Eraña¹, Joaquín Castilla^1,2

¹a CIC bioGUNE, Parque Tecnológico de Bizkaia , Derio , Spain.

|February 2, 2018

Summary

Canine prion protein (PrP) resistance to prion disease is linked to a specific amino acid at codon 163. This finding explains why dogs are resistant to prion infections and has implications for understanding prion disease evolution.

Keywords:

TSE canine PrP evolutionary selection prion resistance

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Area of Science:

Neuroscience
Molecular Biology
Veterinary Science

Background:

Prion diseases are transmissible neurodegenerative disorders.
Species susceptibility to prion diseases has been historically classified, but in vitro and transgenic models have refined this understanding.
The Canidae family exhibits unexpected resistance to prion infections.

Purpose of the Study:

To investigate the molecular determinants of prion resistance in the Canidae family.
To identify specific residues in the canine prion protein (PrP) responsible for this resistance.

Main Methods:

Sequence analysis of canine PrP.
In silico structural analysis.
Cell-free prion replication assays (PMCA).
Generation and testing of transgenic mouse models.

Main Results:

A specific amino acid substitution (aspartic or glutamic acid) at codon 163 of the canid PrP was identified as a key factor inhibiting prion replication in vitro.
Transgenic mice expressing this canine PrP substitution were resistant to infection with various mouse prion strains.
This protective substitution appears to be exclusive to the Canidae family.

Conclusions:

The presence of aspartic or glutamic acid at codon 163 of canid PrP is a major determinant of resistance to prion infection.
This resistance mechanism may have been evolutionarily selected in canids due to their diet.
Understanding species-specific resistance can inform prion disease research and management.