GFP-tagged prion protein is correctly localized and functionally active in the brains of transgenic mice

Sami Barmada, Pedro Piccardo, Keiji Yamaguchi, Bernardino Ghetti, David A. Harris

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Prion diseases result from conversion of PrP C, a neuronal membrane glycoprotein of unknown function, into PrP Sc, an abnormal conformer that is thought to be infectious. To facilitate analysis of PrP distribution in the brain, we have generated transgenic mice in which a PrP promoter drives expression of PrP-EGFP, a fusion protein consisting of enhanced green fluorescent protein inserted adjacent to the glycolipid attachment site of PrP. We find that PrP-EGFP in the brain is glycosylated and glycolipid-anchored and is localized to the surface membrane and the Golgi apparatus of neurons. Like endogenous PrP, PrP-EGFP is concentrated in synapse-rich regions and along axon tracts. PrP-EGFP is functional in vivo, since it ameliorates the cerebellar neurodegeneration induced by a truncated form of PrP. These observations clarify uncertainties in the cellular localization of PrP C in brain, and they establish PrP-EGFP transgenic mice as useful models for further studies of prion biology.

Original languageEnglish
Pages (from-to)527-537
Number of pages11
JournalNeurobiology of Disease
Volume16
Issue number3
DOIs
StatePublished - Aug 2004

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Transgenic Mice
Glycolipids
Brain
Prion Diseases
Prions
Membrane Glycoproteins
Golgi Apparatus
Synapses
Uncertainty
Axons
Neurons
Membranes
Prion Proteins
Proteins
enhanced green fluorescent protein

Keywords

  • Brain
  • Golgi apparatus
  • Prion

ASJC Scopus subject areas

  • Neurology

Cite this

GFP-tagged prion protein is correctly localized and functionally active in the brains of transgenic mice. / Barmada, Sami; Piccardo, Pedro; Yamaguchi, Keiji; Ghetti, Bernardino; Harris, David A.

In: Neurobiology of Disease, Vol. 16, No. 3, 08.2004, p. 527-537.

Research output: Contribution to journalArticle

Barmada, Sami ; Piccardo, Pedro ; Yamaguchi, Keiji ; Ghetti, Bernardino ; Harris, David A. / GFP-tagged prion protein is correctly localized and functionally active in the brains of transgenic mice. In: Neurobiology of Disease. 2004 ; Vol. 16, No. 3. pp. 527-537.
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