Silent Propagation of Classical Scrapie Prions in Homozygous KTransgenic Mice.

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 QK, are linked to resistance, specific breeding programs have not been implemented. Hemizygous transgenic mice carrying the goat Kcellular prion protein (PrP) allele (K-Tg516) exhibited resistance to several classical scrapie isolates. We inoculated homozygous K-Tg516 and Q-Tg501 mice with various scrapie isolates. Homozygous K-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 Q-Tg501 mice. Histologically, K-Tg516 brains lacked prion-related lesions, except for the presence of few isolated scrapie PrP plaques in cases of isolates highly adapted to the K-PrPenvironment. 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.