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Prominent axonopathy in the brain and spinal cord of transgenic mice overexpressing four-repeat human tau protein

Kurt Spittaels, Chris Van den Haute, Jo Van Dorpe UGent, Koen Bruynseels, Kris Vandezande, Isabelle Laenen, Hugo Geerts, Marc Mercken, Raf Sciot, Alfons Van Lommel, et al. (1999) AMERICAN JOURNAL OF PATHOLOGY. 155(6). p.2153-2165
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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
MOTOR-NEURON DISEASE, NERVOUS-SYSTEM, MULTIPLE SYSTEM TAUOPATHY, MONOCLONAL-ANTIBODY, MICROTUBULE-ASSOCIATED PROTEINS, AMYOTROPHIC-LATERAL-SCLEROSIS, ALZHEIMER NEUROFIBRILLARY TANGLES, PAIRED HELICAL FILAMENTS, PRESENILE-DEMENTIA, FRONTOTEMPORAL DEMENTIA
journal title
AMERICAN JOURNAL OF PATHOLOGY
Am. J. Pathol.
volume
155
issue
6
pages
2153 - 2165
Web of Science type
Article
Web of Science id
000084092800040
ISSN
0002-9440
DOI
10.1016/S0002-9440(10)65533-2
language
English
UGent publication?
no
classification
A1
additional info
the first three authors contributed equally to this work
copyright statement
I have transferred the copyright for this publication to the publisher
id
5940802
handle
http://hdl.handle.net/1854/LU-5940802
date created
2015-04-22 10:32:33
date last changed
2017-05-08 08:33:08
@article{5940802,
  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.},
  author       = {Spittaels, Kurt and Van den Haute, Chris and Van Dorpe, Jo and Bruynseels, Koen and Vandezande, Kris and Laenen, Isabelle and Geerts, Hugo and Mercken, Marc and Sciot, Raf and Van Lommel, Alfons and Loos, Ruth and Van Leuven, Fred},
  issn         = {0002-9440},
  journal      = {AMERICAN JOURNAL OF PATHOLOGY},
  keyword      = {MOTOR-NEURON DISEASE,NERVOUS-SYSTEM,MULTIPLE SYSTEM TAUOPATHY,MONOCLONAL-ANTIBODY,MICROTUBULE-ASSOCIATED PROTEINS,AMYOTROPHIC-LATERAL-SCLEROSIS,ALZHEIMER NEUROFIBRILLARY TANGLES,PAIRED HELICAL FILAMENTS,PRESENILE-DEMENTIA,FRONTOTEMPORAL DEMENTIA},
  language     = {eng},
  number       = {6},
  pages        = {2153--2165},
  title        = {Prominent axonopathy in the brain and spinal cord of transgenic mice overexpressing four-repeat human tau protein},
  url          = {http://dx.doi.org/10.1016/S0002-9440(10)65533-2},
  volume       = {155},
  year         = {1999},
}

Chicago
Spittaels, Kurt, Chris Van den Haute, Jo Van Dorpe, Koen Bruynseels, Kris Vandezande, Isabelle Laenen, Hugo Geerts, et al. 1999. “Prominent Axonopathy in the Brain and Spinal Cord of Transgenic Mice Overexpressing Four-repeat Human Tau Protein.” American Journal of Pathology 155 (6): 2153–2165.
APA
Spittaels, Kurt, Van den Haute, C., Van Dorpe, J., Bruynseels, K., Vandezande, K., Laenen, I., Geerts, H., et al. (1999). Prominent axonopathy in the brain and spinal cord of transgenic mice overexpressing four-repeat human tau protein. AMERICAN JOURNAL OF PATHOLOGY, 155(6), 2153–2165.
Vancouver
1.
Spittaels K, Van den Haute C, Van Dorpe J, Bruynseels K, Vandezande K, Laenen I, et al. Prominent axonopathy in the brain and spinal cord of transgenic mice overexpressing four-repeat human tau protein. AMERICAN JOURNAL OF PATHOLOGY. 1999;155(6):2153–65.
MLA
Spittaels, Kurt, Chris Van den Haute, Jo Van Dorpe, et al. “Prominent Axonopathy in the Brain and Spinal Cord of Transgenic Mice Overexpressing Four-repeat Human Tau Protein.” AMERICAN JOURNAL OF PATHOLOGY 155.6 (1999): 2153–2165. Print.