Neuron-specific expression of a hamster prion protein minigene in transgenic mice induces susceptibility to hamster scrapie agent

Richard E. Race, Suzette A. Priola, Richard A. Bessen, Darwin Ernst, Janel Dockter, Glenn F. Rall, Lennart Mucke, Bruce Chesebro, Michael B.A. Oldstone

Research output: Contribution to journalArticlepeer-review

139 Scopus citations

Abstract

To study the effect of cell type-restricted hamster PrP expression on susceptibility to the hamster scrapie agent, we generated transgenic mice using a 1 kb hamster cDNA clone containing the 0.76 kb HPrP open reading frame under control of the neuron-specific enolase promoter. In these mice, expression of HPrP was detected only in brain tissue, with highest levels found in neurons of the cerebellu, hippocampus, thalamus, and cerebral cortex. These transgenic mice were susceptible to infection by the 263K strain of hamster scrapie with an average incubation period of 93 days, compared to 72 days in normal hamsters. In contrast, nontransgenic mice were not susceptible to this agent. These results indicate that neuron-specific expression of the 1 kb HPrP minigene including the HPrP open-reading frame is sufficient to mediate susceptibility to hamster scraple, and that HPrP expression in nonneuronal brain cells is not necessary to overcome the TSE species barrier.

Original languageEnglish
Pages (from-to)1183-1191
Number of pages9
JournalNeuron
Volume15
Issue number5
DOIs
StatePublished - Nov 1995

Keywords

  • Animals
  • Base Sequence
  • Cerebellum/chemistry
  • Cerebral Cortex/chemistry
  • Cricetinae
  • DNA/chemistry
  • Dentate Gyrus/chemistry
  • Gene Expression
  • Genetic Predisposition to Disease
  • Hippocampus/chemistry
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Neurons/metabolism
  • Prions/genetics
  • RNA, Messenger/analysis
  • Scrapie/genetics
  • Thalamus/chemistry

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