Expression of doppel in the CNS of mice does not modulate transmissible spongiform encephalopathy disease

Nadia L Tuzi, Elaine Gall, David Melton, Jean C Manson

Research output: Contribution to journalArticlepeer-review

Abstract

Late onset ataxia reported in three independently derived PrP null lines of mice has been attributed to the overexpression of the doppel protein in the CNS of these mice rather than to the loss of PrP. The central role of PrP in the transmissible spongiform encephalopathies (TSEs), the proximity of the gene which encodes doppel (Prnd) to the PrP gene (Prnp) and the structural similarity shared by PrP and doppel have led to the proposition that ataxia which develops during TSE disease could, in part, be due to doppel. In order to address this hypothesis, we have crossed our two inbred lines of PrP null mice, which either express (RCM) or do not express (NPU) the Prnd gene in the CNS, with mice expressing two Prnp(a[108F189V]) alleles of the PrP gene. We have found that the TSE infection does not influence the level of expression of Prnd in the CNS at the terminal stages of disease. Moreover, we have demonstrated that the level of expression of Prnd in the CNS has no influence on the incubation period, vacuolar pathology nor amount or distribution of PrP(Sc) deposition in the brains of the TSE-infected mice. Doppel has therefore no apparent influence on the outcome of TSE disease in transgenic mice, suggesting it is unlikely to be involved in the naturally occurring TSE diseases in other species.
Original languageEnglish
Pages (from-to)705-11
Number of pages7
JournalJournal of General Virology
Volume83
Issue numberPt 3
Publication statusPublished - Mar 2002

Keywords

  • Alleles
  • Animals
  • Ataxia
  • Blotting, Northern
  • Brain
  • Crosses, Genetic
  • Female
  • GPI-Linked Proteins
  • Gene Deletion
  • Gene Expression
  • Hippocampus
  • Male
  • Mice
  • Mice, Knockout
  • Neurons
  • PrPSc Proteins
  • Prion Diseases
  • Prions
  • RNA, Messenger
  • Thalamus
  • Time Factors

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