title: Deletion of endogenous Tau proteins is not detrimental in Drosophila.
abstract: Human Tau (hTau) is a highly soluble and natively unfolded protein that binds to microtubules within neurons. Its dysfunction and aggregation into insoluble paired helical filaments is involved in the pathogenesis of Alzheimer's disease (AD), constituting, together with accumulated β-amyloid (Aβ) peptides, a hallmark of the disease. Deciphering both the loss-of-function and toxic gain-of-function of hTau proteins is crucial to further understand the mechanisms leading to neurodegeneration in AD. As the fruit fly Drosophila melanogaster expresses Tau proteins (dTau) that are homologous to hTau, we aimed to better comprehend dTau functions by generating a specific tau knock-out (KO) fly line using homologous recombination. We observed that the specific removal of endogenous dTau proteins did not lead to overt, macroscopic phenotypes in flies. Indeed, survival, climbing ability and neuronal function were unchanged in tau KO flies. In addition, we did not find any overt positive or negative effect of dTau removal on human Aβ-induced toxicity. Altogether, our results indicate that the absence of dTau proteins has no major functional impact on flies, and suggests that our tau KO strain is a relevant model to further investigate the role of dTau proteins in vivo, thereby giving additional insights into hTau functions.
authors.affiliation: Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Strasse 9b, 50931 Cologne, Germany.|CECAD Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, 50931 Cologne, Germany.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Burnouf
authors.affiliation: Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Strasse 9b, 50931 Cologne, Germany.|CECAD Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, 50931 Cologne, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Grönke
authors.affiliation: Institute of Healthy Ageing, Department of Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, London, WC1E 6BT, UK.
authors.forename: Hrvoje
authors.initials: H
authors.lastname: Augustin
authors.affiliation: Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Strasse 9b, 50931 Cologne, Germany.|CECAD Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, 50931 Cologne, Germany.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Dols
authors.affiliation: Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Strasse 9b, 50931 Cologne, Germany.|CECAD Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, 50931 Cologne, Germany.
authors.forename: Marianna Karina
authors.initials: MK
authors.lastname: Gorsky
authors.affiliation: Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Strasse 9b, 50931 Cologne, Germany.|CECAD Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, 50931 Cologne, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Werner
authors.affiliation: Institute of Healthy Ageing, Department of Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, London, WC1E 6BT, UK.
authors.forename: Fiona
authors.initials: F
authors.lastname: Kerr
authors.affiliation: Institute of Healthy Ageing, Department of Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, London, WC1E 6BT, UK.
authors.forename: Nazif
authors.initials: N
authors.lastname: Alic
authors.affiliation: Institute of Healthy Ageing, Department of Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, London, WC1E 6BT, UK.
authors.forename: Pedro
authors.initials: P
authors.lastname: Martinez
authors.affiliation: Max Planck Institute for Biology of Ageing, Joseph-Stelzmann-Strasse 9b, 50931 Cologne, Germany.|CECAD Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases, 50931 Cologne, Germany.|Institute of Healthy Ageing, Department of Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, London, WC1E 6BT, UK.
authors.forename: Linda
authors.initials: L
authors.lastname: Partridge
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D030801:Animals, Genetically Modified; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000502:physiology; D055785:Gene Knockdown Techniques; D008017:Life Expectancy; D008124:Locomotion; D009474:Neurons / Q000502:physiology; D016875:tau Proteins / Q000235:genetics*
chemical_list: D016229:Amyloid beta-Peptides; D029721:Drosophila Proteins; D016875:tau Proteins