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Rat tau proteome consists of six tau isoforms: implication for animal models of human tauopathies
Abstract
Human brain encompasses six tau isoforms, containing either three (3R) or four (4R) repeat domains, all of which participate in the pathogenesis of human tauopathies. To investigate the role of tau protein in the disease, transgenic rat models have been created. However, unlike humans, it has been suggested that rat brain expresses only three 4R tau isoforms. Because of the significance of the number of tau isoforms for faithful reproducibility of neurofibrillary pathology in transgenic rat models, we reopened this issue. Surprisingly, our results showed that adult rat brain contains six tau isoforms like humans. Protein expression of 4R tau isoforms was ninefold higher than 3R isoforms. Furthermore, the protein levels of tau isoforms with none, one or two N‐terminal inserts were 30%, 35%, and 35% of total tau, respectively. Moreover, amount and ratio of tau isoforms were developmentally regulated. The levels of 4R tau isoforms progressively increased from early postnatal period until adulthood, whereas the expression of 3R tau isoforms reached maximum at P10 and then gradually declined. Our results show that rat brain encompasses full tau proteome similar to humans. These findings support the use of rat as an animal model in human tauopathies research.
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“Adult human and rat brains express both 3R and 4R Tau isoforms [28]: in contrast, adult mouse brains express only 4R tau [29]”
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Metadata
- Authors
- Hanes, J., Zilka, N., Bartkova, M., Caletkova, M., Dobrota, D., & Novak, M.
- Affiliations
- Slovak Academy of Sciences (SK)
- ORCID
- Hanes, Jozef
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2009-02-09
- Volume
- 108
- Issue
- 5
- Pages
- 1167-1176
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2027284964
- Cited by
- 109
- References
- 58
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 9 · 2023: 9 · 2022: 8 · 2021: 13 · 2020: 9 · 2019: 1 · 2018: 5 · 2017: 5 · 2016: 8 · 2015: 11 · 2014: 3 · 2013: 5
- FWCI
- 1.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Vedecká Grantová Agentúra MŠVVaŠ SR a SAV
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- tau protein, tau isoforms, tauopathy, transgenic rats, neurofibrillary tangles, animal models of neurodegenerative disease
- MeSH terms
- Age Factors, Animals, Brain, Disease Models, Animal, Humans, Rats, Inbred SHR, Electrophoresis, Gel, Two-Dimensional, tau Proteins, Gene Expression Regulation, Developmental, Protein Isoforms, Proteome, Tauopathies, Rats
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