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Title: Prominent axonopathy in the brain and spinal cord of transgenic mice overexpressing four-repeat human tau protein
Authors: Spittaels, K
Van Den Haute, Chris
Van Dorpe, Jo
Bruynseels, K
Vandezande, K
Laenen, Isabel
Geerts, H
Mercken, Marc
Sciot, Raphael
Van Lommel, Alfons
Loos, R
Van Leuven, Freddy #
Issue Date: Dec-1999
Series Title: American Journal of Pathology vol:155 issue:6 pages:2153-65
Abstract: Mutations in the human tau gene cause frontotemporal dementia and parkinsonism linked to chromosome 17. Some mutations, including mutations in intron 10, induce increased levels of the functionally normal four-repeat tau protein isoform, leading to neurodegeneration. We generated transgenic mice that overexpress the four-repeat human tau protein isoform specifically in neurons. The transgenic mice developed axonal degeneration in brain and spinal cord. In the model, axonal dilations with accumulation of neurofilaments, mitochondria, and vesicles were documented. The axonopathy and the accompanying dysfunctional sensorimotor capacities were transgene-dosage related. These findings proved that merely increasing the concentration of the four-repeat tau protein isoform is sufficient to injure neurons in the central nervous system, without formation of intraneuronal neurofibrillary tangles. Evidence for astrogliosis and ubiquitination of accumulated proteins in the dilated part of the axon supported this conclusion. This transgenic model, overexpressing the longest isoform of human tau protein, recapitulates features of known neurodegenerative diseases, including Alzheimer's disease and other tauopathies. The model makes it possible to study the interaction with additional factors, to be incorporated genetically, or with other biological triggers that are implicated in neurodegeneration.
URI: 
ISSN: 0002-9440
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Translational Cell & Tissue Research
Associated Laboratories - miscellaneous (-)
Research Group for Neurobiology and Gene Therapy
Department of Human Genetics - miscellaneous
# (joint) last author

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