PUBLICATION

Human TAUP301L overexpression results in TAU hyperphosphorylation without neurofibrillary tangles in adult zebrafish brain.

Authors
Cosacak, M.I., Bhattarai, P., Bocova, L., Dzewas, T., Mashkaryan, V., Papadimitriou, C., Brandt, K., Hollak, H., Antos, C.L., Kizil, C.
ID
ZDB-PUB-171013-14
Date
2017
Source
Scientific Reports   7: 12959 (Journal)
Registered Authors
Antos, Christopher, Bhattarai, Prabesh, Brandt, Kerstin, Cosacak, Mehmet Ilyas, Hollak, Heike, Kizil, Caghan, Papadimitriou, Christos
Keywords
none
MeSH Terms
  • Phenotype
  • Mutant Proteins/metabolism*
  • Models, Biological
  • Stem Cells/metabolism
  • Inflammation/pathology
  • Larva/metabolism
  • Humans
  • Behavior, Animal
  • Neurons/metabolism
  • Phosphorylation
  • Aging/metabolism*
  • Animals
  • Brain/metabolism*
  • Proliferating Cell Nuclear Antigen/metabolism
  • Neurofibrillary Tangles/metabolism*
  • Zebrafish/metabolism*
  • Amyloid beta-Peptides/toxicity
  • Protein Multimerization
  • tau Proteins/metabolism*
  • Cell Death
  • Animals, Genetically Modified
  • Nerve Regeneration/drug effects
(all 22)
PubMed
29021554 Full text @ Sci. Rep.
Abstract
Microtubule-associated TAU protein is a pathological hallmark in Alzheimer's disease (AD), where hyperphosphorylation of TAU generates neurofibrillary tangles. To investigate the effects of TAU in a regenerative adult vertebrate brain system, we generated a cre/lox-based transgenic model of zebrafish that chronically expresses human TAUP301L, which is a variant of human TAU protein that forms neurofibrillary tangles in mouse models and humans. Interestingly, we found that although chronic and abundant expression of TAUP301L starting from early embryonic development led to hyperphosphorylation, TAUP301L did not form oligomers and neurofibrillary tangles, and did not cause elevated apoptosis and microglial activation, which are classical symptoms of tauopathies in mammals. Additionally, TAUP301L neither increased neural stem cell proliferation nor activated the expression of regenerative factor Interleukin-4, indicating that TAUP301L toxicity is prevented in the adult zebrafish brain. By combining TAUP301L expression with our established Aβ42 toxicity model, we found that Aβ42 ceases to initiate neurofibrillary tangle formation by TAUP301L, and TAUP301L does not exacerbate the toxicity of Aβ42. Therefore, our results propose a cellular mechanism that protects the adult zebrafish brain against tauopathies, and our model can be used to understand how TAU toxicity can be prevented in humans.
Genes / Markers
Figures
Figure Gallery (16 images) / 2
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
ced1Tgchemical treatment by injection: amyloid-beta polypeptide 42, chemical treatment by environment: tamoxifenAdult
ced1Tgchemical treatment by injection: amyloid-beta polypeptide 42, chemical treatment by environment: tamoxifenAdult
ced1Tg; ced2Tgchemical treatment by injection: amyloid-beta polypeptide 42, chemical treatment by environment: tamoxifenAdult
ced1Tg; ced2Tgchemical treatment by injection: amyloid-beta polypeptide 42, chemical treatment by environment: tamoxifenAdult
ced1Tg; ced2Tgchemical treatment by injection: amyloid-beta polypeptide 42, chemical treatment by environment: tamoxifenAdult
ced1Tg; ced2Tgchemical treatment by injection: amyloid-beta polypeptide 42, chemical treatment by environment: tamoxifenAdult
ced1Tg; ced2Tgchemical treatment by environment: tamoxifenAdult
ced1Tg; ced2Tgchemical treatment by environment: tamoxifenAdult
ced1Tg; ced2Tgchemical treatment by environment: tamoxifenAdult
ced1Tg; ced2Tgchemical treatment by environment: tamoxifenAdult
1 - 10 of 11
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ced1TgTransgenic Insertion
    ced2TgTransgenic Insertion
      tud106TgTransgenic Insertion
        1 - 3 of 3
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        Human Disease / Model
        Sequence Targeting Reagents
        No data available
        Fish
        1 - 3 of 3
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        Antibodies
        Orthology
        No data available
        Engineered Foreign Genes
        Marker Marker Type Name
        CreEFGCre
        DsRedEFGDsRed
        GFPEFGGFP
        mCherryEFGmCherry
        1 - 4 of 4
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        Mapping
        No data available