Prion protein devoid of the octapeptide repeat region restores susceptibility to scrapie in PrP knockout mice

Mice devoid of PrP are resistant to scrapie and fail to replicate the agent . Introduction of transgenes expressing PrP into such mice restores suscept ibility to scrapie. We find that truncated PrP devoid of the five copper bi nding octarepeats still sustains scrapie infection; however, incubation tim es are longer and prion titers and protease-resistant PrP are about 30-fold lower than in wild-type mice. Surprisingly, brains of terminally ill anima ls show no histopathology typical for scrapie. However, in the spinal cord, infectivity, gliosis, and motor neuron loss are as in scrapie-infected wil d-type controls. Thus, while the region comprising the octarepeats is not e ssential for mediating pathogenesis and prion replication, it modulates the extent of these events and of disease presentation.