Oligodendroglial tau filament formation in transgenic mice expressing G272V tau

Gotz, Jürgen, Tolnay, Markus, Barmettler, Robi, Chen, Feng, Probst, Alphonse and Nitsch, Roger M. (2001) Oligodendroglial tau filament formation in transgenic mice expressing G272V tau. European Journal of Neuroscience, 13 11: 2131-2140. doi:10.1046/j.0953-816X.2001.01604.x


Author Gotz, Jürgen
Tolnay, Markus
Barmettler, Robi
Chen, Feng
Probst, Alphonse
Nitsch, Roger M.
Title Oligodendroglial tau filament formation in transgenic mice expressing G272V tau
Journal name European Journal of Neuroscience   Check publisher's open access policy
ISSN 0953-816X
1460-9568
Publication date 2001-01-01
Year available 2001
Sub-type Article (original research)
DOI 10.1046/j.0953-816X.2001.01604.x
Open Access Status Not Open Access
Volume 13
Issue 11
Start page 2131
End page 2140
Total pages 10
Place of publication Chichester, West Sussex United Kingdom
Publisher Wiley-Blackwell Publishing
Language eng
Formatted abstract
Genetic evidence indicates that several mutations in tau, including G272V, are linked to frontotemporal dementia with parkinsonism. We expressed this mutation in mouse brains by combining a prion protein promoter-driven expression system with an autoregulatory transactivator loop that resulted in high expression of human G272V tau in neurons and in oligodendrocytes. We show that G272V tau can form filaments in murine oligodendrocytes. Electron microscopy established that the filaments were either straight or had a twisted structure; these were 17–20 nm wide and had a periodicity of ≈ 75 nm. Filament formation was associated with tau phosphorylation at distinct sites, including the AT8 epitope 202/205 in vivo. Immunogold electron microscopy of sarcosyl-extracted spinal cords from G272V transgenic mice using phosphorylation-dependent antibodies AT8 or AT100 identified several sparsely gold-labelled 6-nm filaments. In the spinal cord, fibrillary inclusions were also identified by thioflavin-S fluorescent microscopy in oligodendrocytes and motor neurons. These results establish that expression of the G272V mutation in mice causes oligodendroglial fibrillary lesions that are similar to those seen in human tauopathies.
Keyword Alzheimer's disease
Frontotemporal dementia
Phosphorylation
Transactivator
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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Created: Thu, 27 Feb 2014, 19:10:54 EST by Ms Kate Rowe on behalf of Clem Jones Centre for Ageing Dementia Research