A single amino acid alteration (101L) introduced into murine PrP dramatically alters incubation time of transmissible spongiform encephalopathy

J C Manson, E Jamieson, H Baybutt, N L Tuzi, R Barron, I McConnell, R Somerville, J Ironside, R Will, M S Sy, D W Melton, J Hope, C Bostock

Research output: Contribution to journalArticlepeer-review

Abstract

A mutation equivalent to P102L in the human PrP gene, associated with Gerstmann-Straussler syndrome (GSS), has been introduced into the murine PrP gene by gene targeting. Mice homozygous for this mutation (101LL) showed no spontaneous transmissible spongiform encephalopathy (TSE) disease, but had incubation times dramatically different from wild-type mice following inoculation with different TSE sources. Inoculation with GSS produced disease in 101LL mice in 288 days. Disease was transmitted from these mice to both wild-type (226 days) and 101LL mice (148 days). In contrast, 101LL mice infected with ME7 had prolonged incubation times (338 days) compared with wild-type mice (161 days). The 101L mutation does not, therefore, produce any spontaneous genetic disease in mice but significantly alters the incubation time of TSE infection. Additionally, a rapid TSE transmission was demonstrated despite extremely low levels of disease-associated PrP.
Original languageEnglish
Pages (from-to)6855-64
Number of pages10
JournalEMBO Journal
Volume18
Issue number23
DOIs
Publication statusPublished - 1 Dec 1999

Keywords

  • Alleles
  • Animals
  • Blotting, Southern
  • Blotting, Western
  • Brain
  • Disease Transmission, Infectious
  • Gerstmann-Straussler-Scheinker Disease
  • Heterozygote
  • Homozygote
  • Humans
  • Immunohistochemistry
  • Mice
  • Mice, Transgenic
  • Mutation
  • Prion Diseases
  • Prions
  • Time Factors

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