Publication

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

Journal Paper/Review - Aug 1, 2000

Units
PubMed

Citation
Flechsig E, Shmerling D, Hegyi I, Raeber A, Fischer M, Cozzio A, von Mering C, Aguzzi A, Weissmann C. Prion protein devoid of the octapeptide repeat region restores susceptibility to scrapie in PrP knockout mice. Neuron 2000; 27:399-408.
Type
Journal Paper/Review (English)
Journal
Neuron 2000; 27
Publication Date
Aug 1, 2000
Issn Print
0896-6273
Pages
399-408
Brief description/objective

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