Inherited prion disease caused by the V210I mutation: Transmission to transgenic mice

J. A. Mastrianni, S. Capellari, G. C. Telling, D. Han, P. Bosque, S. B. Prusiner, S. J. DeArmond

Research output: Contribution to journalArticle

Abstract

Objective: To describe the clinical and neuropathologic profile and determine the strain characteristics of familial Creutzfeldt-Jakob disease (fCJD) caused by a point mutation of the PRNP gene at codon 210 that results in a valine-to-isoleucine substitution in the prion protein (PrP). Methods: The clinicopathologic features of four individuals from the United States who died of fCJD(V210I) were compared. Transgenic (Tg) mice expressing a chimeric human-mouse PrP transgene were inoculated with brain extracts from three fCJD(E210I) cases, sporadic CJD (sCJD), fCJD(E200K), and fatal familial insomnia (FFI), to compare prion strain characteristics. Results: The clinicopathologic profile of fCJD(V210I) was variable among cases but shared similarities with sCJD. The pattern of PrPSc deposition in the brains of Tg mice was similar to that caused by sCJD but different from that associated with fCJD(E200K) or FFI. Conclusions: Each of these prion diseases is characterized by a rapidly progressive dementia with myoclonus, periodic complexes on EEG, and spongiform change without PrP plaque deposition in the brain. The occurrence of a different PrPSc phenotype with each PRNP mutation argues that each respective amino acid sequence substitution produces a different prion strain.

Original languageEnglish
Pages (from-to)2198-2205
Number of pages8
JournalNeurology
Volume57
Issue number12
Publication statusPublished - Dec 26 2001

ASJC Scopus subject areas

  • Neuroscience(all)

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    Mastrianni, J. A., Capellari, S., Telling, G. C., Han, D., Bosque, P., Prusiner, S. B., & DeArmond, S. J. (2001). Inherited prion disease caused by the V210I mutation: Transmission to transgenic mice. Neurology, 57(12), 2198-2205.