Prion protein and scrapie susceptibility

Area of Science:

• Veterinary Medicine
• Molecular Biology
• Neuroscience

Background:

• Transmissible Spongiform Encephalopathies (TSEs), or prion diseases, are linked to the prion protein (PrP).
• Prion protein polymorphisms are known to affect susceptibility to these neurodegenerative diseases.
• Sheep scrapie is a significant TSE where host genetics play a crucial role.

Purpose of the Study:

• To review current understanding of prion protein's role in TSEs.
• To investigate the impact of prion protein polymorphisms on scrapie susceptibility in sheep.
• To explore the influence of both host and source animal PrP genotypes on scrapie transmission using an in vitro model.

Main Methods:

• Review of current scientific literature on prion protein and TSEs.
• Analysis of sheep prion protein (PrP) genotypes, focusing on polymorphisms at codons 136, 154, and 171.
• Development and utilization of an in vitro system to study sheep PrP variants and their correlation with scrapie susceptibility and transmissibility.

Main Results:

• Sheep PrP genotype is a primary risk factor for scrapie, with specific polymorphisms (codons 136, 154, 171) modulating susceptibility.
• The in vitro system demonstrated that scrapie susceptibility is determined by the target animal's PrP genotype.
• Importantly, the PrP genotype of the source animal also significantly influences scrapie susceptibility, suggesting a role in transmissibility.

Conclusions:

• Prion protein genotype is a critical determinant of scrapie susceptibility in sheep.
• An in vitro model effectively reflects in vivo scrapie susceptibility and highlights the importance of both host and source PrP genotypes.
• The behavior of PrP variants in vitro may serve as a predictive indicator for prion disease transmissibility.