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Mice Lacking Histone Deacetylase 6 Have Hyperacetylated Tubulin but Are Viable and Develop Normally
Open accessAbstract
Posttranslational modifications play important roles in regulating protein structure and function. Histone deacetylase 6 (HDAC6) is a mostly cytoplasmic class II HDAC, which has a unique structure with two catalytic domains and a domain binding ubiquitin with high affinity. This enzyme was recently identified as a multisubstrate protein deacetylase that can act on acetylated histone tails, alpha-tubulin and Hsp90. To investigate the in vivo functions of HDAC6 and the relevance of tubulin acetylation/deacetylation, we targeted the HDAC6 gene by homologous recombination in embryonic stem cells and generated knockout mice. HDAC6-deficient mice are viable and fertile and show hyperacetylated tubulin in most tissues. The highest level of expression of HDAC6 is seen in the testis, yet development and function of this organ are normal in the absence of HDAC6. Likewise, lymphoid development is normal, but the immune response is moderately affected. Furthermore, the lack of HDAC6 results in a small increase in cancellous bone mineral density, indicating that this deacetylase plays a minor role in bone biology. HDAC6-deficient mouse embryonic fibroblasts show apparently normal microtubule organization and stability and also show increased Hsp90 acetylation correlating with impaired Hsp90 function. Collectively, these data demonstrate that mice survive well without HDAC6 and that tubulin hyperacetylation is not detrimental to normal mammalian development.
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“HDAC6, a tubulin deacetylase [24].”
From Elevated SGK1 increases Tau phosphorylation and microtubule instability in Alzheimer’s patient-derived cortical neurons (2026) · cites this paper as [32]
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HDAC6 is a microtubule-associated deacetylase
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HDAC-6 interacts with and deacetylates tubulin and microtubules in vivo
Zhang, Y., Li, N., Caron, C., Matthias, G., Hess, D., Khochbin, S., & Matthias, P. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg115 · Cited by 740 · cited 3×
“Also, disruption of the HDAC6 gene in mouse embryonic stem cells, which led to highly increased tubulin acetylation levels, did not significantly affect cell proliferation or differentiation of these cells (42).”
BackgroundIn vivo destabilization of dynamic microtubules by HDAC6‐mediated deacetylation
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Cited by
Sorted by citations
Haberland, M., Montgomery, R. L., & Olson, E. N. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2485 · Cited by 2,600
“HDAC6 is the main cytoplasmic deacetylase in mammalian cell”
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Metadata
- Authors
- Zhang, Y., Kwon, S., Yamaguchi, T., Cubizolles, F., Rousseaux, S., Kneissel, M., Cao, C., Li, N., Cheng, H.-L., Chua, K., Lombard, D., Mizeracki, A., Matthias, G., Alt, F. W., Khochbin, S., & Matthias, P.
- Affiliations
- Friedrich Miescher Institute (CH)
- Friedrich Miescher Institute for Biomedical Research, Novartis Research Foundation, P.O. Box 2543, Maulbeerstrasse 66, 4058 Basel, Switzerland
- Inserm (FR)
- Novartis (Switzerland) (CH)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Matthias, Patrick
- ORCID
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2008-03-01
- Volume
- 28
- Issue
- 5
- Pages
- 1688-1701
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC2258784
- OpenAlex
- W2162787110
- Cited by
- 559
- References
- 0
- Citations by year
- 2026: 19 · 2025: 28 · 2024: 18 · 2023: 24 · 2022: 37 · 2021: 35 · 2020: 47 · 2019: 32 · 2018: 27 · 2017: 38 · 2016: 24 · 2015: 28 · 2014: 32 · 2013: 33 · 2012: 39
- FWCI
- 13.59
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Ellison Medical Foundation
- Dalhousie University
- Université de Fribourg
- Institut National Du Cancer
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- HDAC6, tubulin acetylation, tubulin deacetylation, alpha-tubulin, HSP90 acetylation, testicular development, lymphoid development, immune response, bone mineral density, microtubule organization, embryonic fibroblasts, post-translational modification, ubiquitin binding
- MeSH terms
- Histone Deacetylase 6, Acetylation, Animals, Cells, Cultured, Crosses, Genetic, Embryo, Mammalian, Female, Fetal Viability, Fibroblasts, Histone Deacetylases, Homozygote, Immunohistochemistry, Male, Mice, Inbred C57BL, Precipitin Tests, Pregnancy, Receptors, Glucocorticoid, Recombination, Genetic, Sperm Count, Spermatogenesis, Testis, Transfection, Tubulin, Absorptiometry, Photon, Bone Density, Gene Deletion, Genes, Reporter, Mice, Knockout, HSP90 Heat-Shock Proteins, Fluorescent Antibody Technique, Indirect, NIH 3T3 Cells, Embryonic Development, Luciferases, Renilla, Mice, Embryonic Stem Cells
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