# Silent Propagation of Classical Scrapie Prions in Homozygous K222 Transgenic Mice

## TL;DR

This study shows that homozygous K222 transgenic mice can silently carry classical scrapie prions without showing symptoms, which could impact breeding programs.

## Contribution

The study reveals silent prion propagation in K222 homozygous mice, challenging assumptions about resistance to classical scrapie.

## Key findings

- Homozygous K222-Tg516 mice did not show clinical signs of scrapie but accumulated prion proteins.
- Few isolated scrapie PrP plaques were observed in mice inoculated with highly adapted isolates.
- Silent carriers could emerge in goat populations if K222 is included in breeding programs.

## Abstract

Classical scrapie affects sheep and goats. To control prevalence in sheep, the European Union initiated breeding programs targeting resilient genotypes. Although certain goat polymorphisms, such as Q222K, are linked to resistance, specific breeding programs have not been implemented. Hemizygous transgenic mice carrying the goat K222 cellular prion protein (PrP) allele (K222-Tg516) exhibited resistance to several classical scrapie isolates. We inoculated homozygous K222-Tg516 and Q222-Tg501 mice with various scrapie isolates. Homozygous K222-Tg516 mice reached the end of their lifespan without exhibiting clinical signs; we observed brain proteinase K–resistant PrP accumulation in those mice that was lower than in Q222-Tg501 mice. Histologically, K222-Tg516 brains lacked prion-related lesions, except for the presence of few isolated scrapie PrP plaques in cases of isolates highly adapted to the K222-PrPC environment. Our findings caution against including that polymorphism in breeding programs, because it could lead to emergence of asymptomatic silent prion carriers of classical scrapie among goat populations.