Onset of ataxia and Purkinje cell loss in PrP null mice inversely correlated with Dpl level in brain

Daniela Rossi, Antonio Cozzio, Eckhard Flechsig, Michael A. Klein, Thomas Rülicke, Adriano Aguzzi, Charles Weissmann

Research output: Contribution to journalArticle

Abstract

PrP knockout mice in which only the open reading frame was disrupted ('Zürich I') remained healthy. However, more extensive deletions resulted in ataxia, Purkinje cell loss and ectopic expression in brain of Doppel (Dpl), encoded by the downstream gene, Prnd. A new PrP knockout line, 'Zürich II', with a 2.9 kb Prnp deletion, developed this phenotype at ∼10 months (50% morbidity). A single Prnp allele abolished the syndrome. Compound Zürich I/Zürich II heterozygotes had half the Dpl of Zürich II mice and developed symptoms 6 months later. Zürich II mice transgenic for a Prnd-containing cosmid expressed Dpl at twice the level and became ataxic ∼5 months earlier. Thus, Dpl levels in brain and onset of the ataxic syndrome are inversely correlated.

Original languageEnglish
Pages (from-to)694-702
Number of pages9
JournalEMBO Journal
Volume20
Issue number4
DOIs
Publication statusPublished - Feb 15 2001

Keywords

  • Cerebellar syndrome
  • Doppel protein
  • Gene deletion
  • Granule cells
  • Prion protein

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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    Rossi, D., Cozzio, A., Flechsig, E., Klein, M. A., Rülicke, T., Aguzzi, A., & Weissmann, C. (2001). Onset of ataxia and Purkinje cell loss in PrP null mice inversely correlated with Dpl level in brain. EMBO Journal, 20(4), 694-702. https://doi.org/10.1093/emboj/20.4.694