Kinetics of prion protein accumulation in the CNS of mice with experimental scrapie

The kinetics of PrP(Sc) and insoluble PrP accumulation in the spleens and brains of CD-1 mice were studied. The mice were inoculated intracerebrally with RML prions and euthanized at various times between inoculation and the onset of illness at approximately 130 days. Protease-resistant PrP(Sc), PrP 27-30, was first detected in brain by histoblotting 49 days after inoculation and by Western immunoblotting at 70 days. In spleen, PrP 27-30 was first detected by Western immunoblotting at 28 days after inoculation. Like PrP 27-30, substantial increases in detergent-insoluble PrP were first detected at 70 days after inoculation in brain and 28 days in spleen. In addition, a progressive increase in detergent-soluble PrP was detected beginning 70 days after inoculation. Further characterization of detergent soluble and insoluble PrP with respect to protease-sensitive PrP(Sc) and prion infectivity will be of considerable interest.