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

(1999) AMERICAN JOURNAL OF PATHOLOGY. 155(6). p.2153-2165
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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.
Keywords
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

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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.
@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},
}

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