Scrapie-infected murine neuroblastoma cells produce protease-resistant prion proteins

D. A. Butler, M. R D Scott, J. M. Bockman, D. R. Borchelt, A. Taraboulos, K. K. Hsiao, D. T. Kingsbury, S. B. Prusiner

Research output: Contribution to journalArticlepeer-review

286 Scopus citations

Abstract

Scrapie and Creutzfeldt-Jakob disease are transmissable, degenerative neurological diseases caused by prions. Considerable evidence argues that prions contain protease-resistant sialoglycoproteins, designated PrP(Sc), encoded by a cellular gene. The prion protein (PrP) gene also encodes a normal cellular protein designated PrP(C). We established clonal cell lines which support the replication of mouse scrapie or Creutzfeldt-Jakob disease prions. Mouse neuroblastoma N2a cells were exposed to mouse scrapie prions and subsequently cloned. After limited proteinase K digestion, three PrP-immunoreactive proteins with apparent molecular masses ranging between 20 and 30 kilodaltons were detected in extracts of scrapie-infected N2a cells by Western (immuno-) blotting. The authenticity of these PrP(Sc) molecules was established by using monospecivic antiserum raised against a synthetic peptide corresponding to a portion of the prion protein. Those clones synthesizing PrP(Sc) molecules possessed scrapie prion infectivity as measured by bioassay; clones without PrP(Sc) failed to demonstrate infectivity. Detection of PrP(Sc) molecules in scrapie-infected N2a cells supports the contention that PrP(Sc) is a component of the infectious scrapie particle and opens new approaches to the study of prion diseases.

Original languageEnglish (US)
Pages (from-to)1558-1564
Number of pages7
JournalJournal of virology
Volume62
Issue number5
DOIs
StatePublished - 1988

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