Inhibition of neuronal maturation in primary hippocampal neurons from tau deficient mice
Abstract
Conflicting evidence supports a role for tau as an essential neuronal cytoskeletal protein or as a redundant protein whose function can be fulfilled by other microtubule-associated proteins. To investigate the function of tau in axonogenesis, we created tau deficient mice by disrupting the TAU gene. The engineered mice do not express the tau protein, appear physically normal and are able to reproduce. In contrast to a previously reported tau knockout mouse, embryonic hippocampal cultures from tau deficient mice show a significant delay in maturation as measured by axonal and neuritic extensions. The classic technique of selectively enhancing axonal growth by growth on laminin substrates failed to restore normal neuronal maturation of tau knockout neurons. By mating human TAU-gene transgenic and tau knockout mice, we reconstituted tau-deficient neurons with human tau proteins and restored a normal pattern of axonal growth and neuronal maturation. The ability of human tau proteins to rescue tau-deficient mouse neurons confirms that tau expression affects the rate of neurite extension.
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Genetic deletion studies indicate that endogenous tau participates in neuronal processes including cytoskeletal regulation, mitochondrial dynamics, synaptic plasticity, network activity, and DNA/RNA stability.
“Genetic deletion studies indicate that endogenous tau participates in a range of neuronal processes, including cytoskeletal regulation, mitochondrial dynamics, synaptic plasticity, network activity [10–22], and stability of DNA and RNA stability [23].”
From Tau Ablation Rewires Brain Cell Programs in Health and Restores Function in Disease (2026) · cites this paper as [10]
In tau knockout brains, no neuronal p-tau staining by VHH-A2-488 was observed, confirming a lack of nonspecific staining of non-tau protein by this nanobody.
“In tau knockout brains (Dawson et al., 2001) we observed no neuronal p-tau staining by VHH-A2-488, confirming a lack of nonspecific staining of non-tau protein by this nanobody (Fig. 1B and Supp. Fig. 1).”
From Spontaneous pathology in PS19 tauopathy mice progresses via brain networks (2025) · cites this paper as Dawson et al., 2001
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Rat hippocampal neurons in dispersed cell culture.
Banker, G. A., & Cowan, W. M. (1977) · Brain Research · doi:10.1016/0006-8993(77)90594-7 · Cited by 1,110 · see citing works
Caceres, A., Banker, G., & Binder, L. (1986) · The Journal of Neuroscience · doi:10.1523/jneurosci.06-03-00714.1986 · Cited by 367 · see citing works
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Alzheimer Disease: An Update on Pathobiology and Treatment Strategies
Long, J. M., & Holtzman, D. M. (2019) · Cell · doi:10.1016/j.cell.2019.09.001 · Cited by 3,204 · see citing works
Reducing Endogenous Tau Ameliorates Amyloid ß-Induced Deficits in an Alzheimer's Disease Mouse Model
Roberson, E. D., Scearce-Levie, K., Palop, J. J., Yan, F., Cheng, I. H., Wu, T., Gerstein, H., Yu, G.-Q., & Mucke, L. (2007) · Science · doi:10.1126/science.1141736 · Cited by 1,892 · see citing works
Palop, J. J., Chin, J., Roberson, E. D., Wang, J., Thwin, M. T., Bien-Ly, N., Yoo, J., Ho, K. O., Yu, G.-Q., Kreitzer, A., et al. (2007) · Neuron · doi:10.1016/j.neuron.2007.07.025 · Cited by 1,653 · see citing works
Tau pathology and neurodegeneration
Spillantini, M. G., & Goedert, M. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70090-5 · Cited by 1,133 · see citing works
Morris, M., Maeda, S., Vossel, K., & Mucke, L. (2011) · Neuron · doi:10.1016/j.neuron.2011.04.009 · Cited by 899 · see citing works
Tau is essential to β-amyloid-induced neurotoxicity
Rapoport, M., Dawson, H. N., Binder, L. I., Vitek, M. P., & Ferreira, A. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.092136199 · Cited by 807 · see citing works
Self-citationArendt, T., Stieler, J. T., & Holzer, M. (2016) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2016.08.018 · Cited by 609 · see citing works
Roberson, E. D., Halabisky, B., Yoo, J. W., Yao, J., Chin, J., Yan, F., Wu, T., Hamto, P., Devidze, N., Yu, G.-Q., et al. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.4152-10.2011 · Cited by 654 · see citing works
Tau phosphorylation in neuronal cell function and dysfunction
Johnson, G. V. W., & Stoothoff, W. H. (2004) · Journal of Cell Science · doi:10.1242/jcs.01558 · Cited by 624 · see citing works
Tau deficiency induces parkinsonism with dementia by impairing APP-mediated iron export
Lei, P., Ayton, S., Finkelstein, D. I., Spoerri, L., Ciccotosto, G. D., Wright, D. K., Wong, B. X. W., Adlard, P. A., Cherny, R. A., Lam, L. Q., et al. (2012) · Nature Medicine · doi:10.1038/nm.2613 · Cited by 594 · see citing works
Caspase-cleavage of tau is an early event in Alzheimer disease tangle pathology
Rissman, R. A., Poon, W. W., Blurton-Jones, M., Oddo, S., Torp, R., Vitek, M. P., LaFerla, F. M., Rohn, T. T., & Cotman, C. W. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200420640 · Cited by 543 · see citing works
Self-citationMorris, M., Knudsen, G. M., Maeda, S., Trinidad, J. C., Ioanoviciu, A., Burlingame, A. L., & Mucke, L. (2015) · Nature Neuroscience · doi:10.1038/nn.4067 · Cited by 472 · see citing works
Antibody against early driver of neurodegeneration cis P-tau blocks brain injury and tauopathy
Kondo, A., Shahpasand, K., Mannix, R., Qiu, J., Moncaster, J., Chen, C.-H., Yao, Y., Lin, Y.-M., Driver, J. A., Sun, Y., et al. (2015) · Nature · doi:10.1038/nature14658 · Cited by 445 · see citing works
Advances in tau-focused drug discovery for Alzheimer's disease and related tauopathies
Brunden, K. R., Trojanowski, J. Q., & Lee, V. M.-Y. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2959 · Cited by 440 · see citing works
Alquezar, C., Arya, S., & Kao, A. W. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2020.595532 · Cited by 367 · see citing works
Yamada, K., Cirrito, J. R., Stewart, F. R., Jiang, H., Finn, M. B., Holmes, B. B., Binder, L. I., Mandelkow, E.-M., Diamond, M. I., Lee, V. M.-Y., et al. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.2569-11.2011 · Cited by 351 · see citing works
Self-citationMummery, C. J., Börjesson-Hanson, A., Blackburn, D. J., Vijverberg, E. G. B., De Deyn, P. P., Ducharme, S., Jonsson, M., Schneider, A., Rinne, J. O., Ludolph, A. C., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02326-3 · Cited by 347 · see citing works
Age-Dependent Impairment of Cognitive and Synaptic Function in the htau Mouse Model of Tau Pathology
Polydoro, M., Acker, C. M., Duff, K., Castillo, P. E., & Davies, P. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.1065-09.2009 · Cited by 329 · see citing works
Andrews-Zwilling, Y., Bien-Ly, N., Xu, Q., Li, G., Bernardo, A., Yoon, S. Y., Zwilling, D., Yan, T. X., Chen, L., & Huang, Y. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.4040-10.2010 · Cited by 326 · see citing works
Tau Protein Is Required for Amyloid β-Induced Impairment of Hippocampal Long-Term Potentiation
Shipton, O. A., Leitz, J. R., Dworzak, J., Acton, C. E. J., Tunbridge, E. M., Denk, F., Dawson, H. N., Vitek, M. P., Wade-Martins, R., Paulsen, O., et al. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.2610-10.2011 · Cited by 315 · see citing works
Self-citationAndreadis, A. (2005) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2004.08.010 · Cited by 311 · see citing works
Role of Amyloid-β and Tau Proteins in Alzheimer’s Disease: Confuting the Amyloid Cascade
Gulisano, W., Maugeri, D., Baltrons, M. A., Fà, M., Amato, A., Palmeri, A., D’Adamio, L., Grassi, C., Devanand, D. P., Honig, L. S., et al. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-179935 · Cited by 313 · see citing works
Dendritic Tau in Alzheimer’s Disease
Ittner, A., & Ittner, L. M. (2018) · Neuron · doi:10.1016/j.neuron.2018.06.003 · Cited by 278 · see citing works
Sydow, A., Van der Jeugd, A., Zheng, F., Ahmed, T., Balschun, D., Petrova, O., Drexler, D., Zhou, L., Rune, G., Mandelkow, E., et al. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.5245-10.2011 · Cited by 302 · see citing works
Zempel, H., Luedtke, J., Kumar, Y., Biernat, J., Dawson, H., Mandelkow, E., & Mandelkow, E. (2013) · The EMBO Journal · doi:10.1038/emboj.2013.207 · Cited by 283 · see citing works
Tau Protein Interaction Partners and Their Roles in Alzheimer’s Disease and Other Tauopathies
Sinsky, J., Pichlerova, K., & Hanes, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179207 · Cited by 220 · see citing works
Maia, L. F., Kaeser, S. A., Reichwald, J., Hruscha, M., Martus, P., Staufenbiel, M., & Jucker, M. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3006446 · Cited by 204 · see citing works
A role for tau at the synapse in Alzheimer’s disease pathogenesis
Pooler, A. M., Noble, W., & Hanger, D. P. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.09.018 · Cited by 203 · see citing works
Prion-like Properties of Tau Protein: The Importance of Extracellular Tau as a Therapeutic Target
Holmes, B. B., & Diamond, M. I. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.r114.549295 · Cited by 202 · see citing works
Tau isoform regulation is region‐ and cell‐specific in mouse brain
McMillan, P., Korvatska, E., Poorkaj, P., Evstafjeva, Z., Robinson, L., Greenup, L., Leverenz, J., Schellenberg, G. D., & D'Souza, I. (2008) · Journal of Comparative Neurology · doi:10.1002/cne.21867 · Cited by 179 · see citing works
Tau reduction prevents Aβ-induced axonal transport deficits by blocking activation of GSK3β
Vossel, K. A., Xu, J. C., Fomenko, V., Miyamoto, T., Suberbielle, E., Knox, J. A., Ho, K., Kim, D. H., Yu, G.-Q., & Mucke, L. (2015) · Journal of Cell Biology · doi:10.1083/jcb.201407065 · Cited by 167 · see citing works
Tau protein binds to pericentromeric DNA: a putative role for nuclear tau in nucleolar organization
Sjöberg, M. K., Shestakova, E., Mansuroglu, Z., Maccioni, R. B., & Bonnefoy, E. (2006) · Journal of Cell Science · doi:10.1242/jcs.02907 · Cited by 166 · see citing works
Antisense oligonucleotides: treating neurodegeneration at the level of RNA
DeVos, S. L., & Miller, T. M. (2013) · Neurotherapeutics · doi:10.1007/s13311-013-0194-5 · Cited by 164 · see citing works
Leroy, K., Ando, K., Laporte, V., Dedecker, R., Suain, V., Authelet, M., Héraud, C., Pierrot, N., Yilmaz, Z., Octave, J.-N., et al. (2012) · The American Journal of Pathology · doi:10.1016/j.ajpath.2012.08.012 · Cited by 161 · see citing works
Accumulation of tau induced in neurites by microglial proinflammatory mediators
Gorlovoy, P., Larionov, S., Pham, T. T. H., & Neumann, H. (2009) · The FASEB Journal · doi:10.1096/fj.08-123877 · Cited by 156 · see citing works
Avila, J., Jiménez, J. S., Sayas, C. L., Bolós, M., Zabala, J. C., Rivas, G., & Hernández, F. (2016) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2016.00262 · Cited by 140 · see citing works
Cognition and hippocampal synaptic plasticity in mice with a homozygous tau deletion
Ahmed, T., Van der Jeugd, A., Blum, D., Galas, M.-C., D’Hooge, R., Buee, L., & Balschun, D. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.05.005 · Cited by 137 · see citing works
Rubenstein, R., Chang, B., Davies, P., Wagner, A. K., Robertson, C. S., & Wang, K. K. W. (2015) · Journal of Neurotrauma · doi:10.1089/neu.2014.3548 · Cited by 116 · see citing works
Axonal degeneration in tauopathies: disease relevance and underlying mechanisms
Kneynsberg, A., Combs, B., Christensen, K., Morfini, G., & Kanaan, N. M. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00572 · Cited by 102 · see citing works
Cheng, J. S., Craft, R., Yu, G.-Q., Ho, K., Wang, X., Mohan, G., Mangnitsky, S., Ponnusamy, R., & Mucke, L. (2014) · PLoS ONE · doi:10.1371/journal.pone.0115765 · Cited by 100 · see citing works
Jiang, S., Maphis, N. M., Binder, J., Chisholm, D., Weston, L., Duran, W., Peterson, C., Zimmerman, A., Mandell, M. A., Jett, S. D., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109720 · Cited by 92 · see citing works
Norambuena, A., Wallrabe, H., McMahon, L., Silva, A., Swanson, E., Khan, S. S., Baerthlein, D., Kodis, E., Oddo, S., Mandell, J. W., et al. (2017) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.08.015 · Cited by 79 · see citing works
Seizure resistance without parkinsonism in aged mice after tau reduction
Li, Z., Hall, A. M., Kelinske, M., & Roberson, E. D. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.05.001 · Cited by 71 · see citing works
Network dysfunction in<i>α</i>‐synuclein transgenic mice and human Lewy body dementia
Morris, M., Sanchez, P. E., Verret, L., Beagle, A. J., Guo, W., Dubal, D., Ranasinghe, K. G., Koyama, A., Ho, K., Yu, G., et al. (2015) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.257 · Cited by 61 · see citing works
Tau-targeting therapy in Alzheimer’s disease: Critical advances and future opportunities
Guo, Y., Li, S., Zeng, L.-H., & Tan, J. (2022) · Ageing and Neurodegenerative Diseases · doi:10.20517/and.2022.16 · Cited by 61 · see citing works
Mechanisms of tau and Aβ-induced excitotoxicity
Pallo, S. P., DiMaio, J., Cook, A., Nilsson, B., & Johnson, G. V. W. (2016) · Brain Research · doi:10.1016/j.brainres.2015.12.048 · Cited by 46 · see citing works
Further understanding of tau phosphorylation: implications for therapy
Medina, M., & Avila, J. (2015) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.2015.1000864 · Cited by 41 · see citing works
Schelle, J., Häsler, L. M., Göpfert, J. C., Joos, T. O., Vanderstichele, H., Stoops, E., Mandelkow, E., Neumann, U., Shimshek, D. R., Staufenbiel, M., et al. (2017) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.09.005 · Cited by 40 · see citing works
Hannan, S. B., Dräger, N. M., Rasse, T. M., Voigt, A., & Jahn, T. R. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13532 · Cited by 38 · see citing works
Neuronal degeneration, synaptic defects, and behavioral abnormalities in tau45-230 transgenic mice
Lang, A. E., Riherd Methner, D. N., & Ferreira, A. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.06.017 · Cited by 35 · see citing works
Self-citationMiyamoto, T., Kim, D., Knox, J. A., Johnson, E., & Mucke, L. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.666529 · Cited by 33 · see citing works
Localization, induction, and cellular effects of tau phosphorylated at threonine 217<sup>1</sup>
Rajbanshi, B., Guruacharya, A., Mandell, J. W., & Bloom, G. S. (2023) · Alzheimer's & Dementia · doi:10.1002/alz.12892 · Cited by 20 · see citing works
Wild-Type, but Not Mutant N296H, Human Tau Restores Aβ-Mediated Inhibition of LTP in Tau−/− mice
Vargas-Caballero, M., Denk, F., Wobst, H. J., Arch, E., Pegasiou, C.-M., Oliver, P. L., Shipton, O. A., Paulsen, O., & Wade-Martins, R. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00201 · Cited by 18 · see citing works
Spontaneous pathology in PS19 tauopathy mice progresses via brain networks
Ramirez, D. M. O., Whitesell, J. D., Bhagwat, N., Thomas, T. L., Ajay, A. D., Nawaby, A., Delatour, B., Bay, S., LaFaye, P., Harris, J. A., et al. (2025) · Neurobiology of Disease · doi:10.1016/j.nbd.2025.107072 · Cited by 5 · see citing works
Nakata, R., Torii, T., Miyasaka, T., & Misonou, H. (2026) · Neuroscience Research · doi:10.1016/j.neures.2025.104987 · Cited by 3 · see citing works
Tau Ablation Rewires Brain Cell Programs in Health and Restores Function in Disease
Chimal-Juárez, E., Patel, H., Jury-Garfe, N., Dabin, L. C., Vidal, R., Kim, J., & Lasagna-Reeves, C. A. (2026) · bioRxiv · doi:10.64898/2026.05.12.724684
- Authors
- Dawson, H. N., Ferreira, A., Eyster, M. V., Ghoshal, N., Binder, L. I., & Vitek, M. P.
- Affiliations
- Duke University (US)
- Northwestern University (US)
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2001-03-15
- Volume
- 114
- Issue
- 6
- Pages
- 1179-1187
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- OpenAlex
- W1893543180
- Cited by
- 527
- References
- 2
- Citations by year
- 2026: 20 · 2025: 22 · 2024: 17 · 2023: 29 · 2022: 25 · 2021: 27 · 2020: 24 · 2019: 24 · 2018: 22 · 2017: 34 · 2016: 37 · 2015: 28 · 2014: 26 · 2013: 31 · 2012: 21
- FWCI
- 5.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cell Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ag015383-02)
- National Institute on Aging (AG15307, AG15383, AG0946)
- National Institute of Neurological Disorders and Stroke (R01NS039080, NS 39080)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Keywords
- tau protein, tau knockout mice, neuronal maturation, axonogenesis, hippocampal neurons, neurite outgrowth, axon growth, laminin substrate, microtubule-associated proteins, tau gene, transgenic rescue
- MeSH terms
- Animals, Axons, Cell Division, Cells, Cultured, Female, Hippocampus, Humans, Laminin, Male, Mice, Inbred C57BL, Microtubule-Associated Proteins, Neurons, Biomarkers, Gene Expression, tau Proteins, Mice, Knockout, Gene Targeting, Mice
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