Prion protein (PrP) with amino-proximal deletions restoring susceptibility of PrP knockout mice to scrapie

EMBO J. 1996 Mar 15;15(6):1255-64.


The 'protein only' hypothesis postulates that the prion, the agent causing transmissible spongiform encephalopathies, is PrP(Sc), an isoform of the host protein PrP(C). Protease treatment of prion preparations cleaves off approximately 60 N-terminal residues of PrP(Sc) but does not abrogate infectivity. Disruption of the PrP gene in the mouse abolishes susceptibility to scrapie and prion replication. We have introduced into PrP knockout mice transgenes encoding wild-type PrP or PrP lacking 26 or 49 amino-proximal amino acids which are protease susceptible in PrP(Sc). Inoculation with prions led to fatal disease, prion propagation and accumulation of PrP(Sc) in mice expressing both wild-type and truncated PrPs. Within the framework of the 'protein only' hypothesis, this means that the amino-proximal segment of PrP(C) is not required either for its susceptibility to conversion into the pathogenic, infectious form of PrP or for the generation of PrP(Sc).

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amyloid / deficiency
  • Amyloid / genetics
  • Animals
  • Base Sequence
  • Brain / anatomy & histology
  • Disease Susceptibility
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Mutation
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics*
  • PrPC Proteins / genetics
  • PrPSc Proteins / biosynthesis
  • PrPSc Proteins / genetics
  • Prion Proteins
  • Prions / biosynthesis
  • Prions / genetics*
  • Protein Precursors / deficiency
  • Protein Precursors / genetics
  • RNA, Messenger / isolation & purification
  • Scrapie / etiology
  • Scrapie / genetics*
  • Scrapie / transmission
  • Sequence Deletion


  • Amyloid
  • Nerve Tissue Proteins
  • PrPC Proteins
  • PrPSc Proteins
  • Prion Proteins
  • Prions
  • Prnp protein, mouse
  • Protein Precursors
  • RNA, Messenger