Mice lacking histone deacetylase 6 have hyperacetylated tubulin but are viable and develop normally

Yu Zhang, So Hee Kwon, Teppei Yamaguchi, Fabien Cubizolles, Sophie Rousseaux, Michaela Kneissel, Chun Cao, Na Li, Hwei Ling Cheng, Katrin Chua, David Lombard, Adam Mizeracki, Gabriele Matthias, Frederick W. Alt, Saadi Khochbin, Patrick Matthias

Research output: Contribution to journalArticle

316 Citations (Scopus)

Abstract

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, α-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.

Original languageEnglish
Pages (from-to)1688-1701
Number of pages14
JournalMolecular and Cellular Biology
Volume28
Issue number5
DOIs
Publication statusPublished - 2008 Mar

Fingerprint

Histone Deacetylases
Tubulin
Acetylation
Homologous Recombination
Post Translational Protein Processing
Embryonic Stem Cells
Ubiquitin
Knockout Mice
Microtubules
Histones
Bone Density
Tail
Testis
Catalytic Domain
Proteins
Fibroblasts
Bone and Bones

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Zhang, Yu ; Kwon, So Hee ; Yamaguchi, Teppei ; Cubizolles, Fabien ; Rousseaux, Sophie ; Kneissel, Michaela ; Cao, Chun ; Li, Na ; Cheng, Hwei Ling ; Chua, Katrin ; Lombard, David ; Mizeracki, Adam ; Matthias, Gabriele ; Alt, Frederick W. ; Khochbin, Saadi ; Matthias, Patrick. / Mice lacking histone deacetylase 6 have hyperacetylated tubulin but are viable and develop normally. In: Molecular and Cellular Biology. 2008 ; Vol. 28, No. 5. pp. 1688-1701.
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abstract = "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, α-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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Zhang, Y, Kwon, SH, Yamaguchi, T, Cubizolles, F, Rousseaux, S, Kneissel, M, Cao, C, Li, N, Cheng, HL, Chua, K, Lombard, D, Mizeracki, A, Matthias, G, Alt, FW, Khochbin, S & Matthias, P 2008, 'Mice lacking histone deacetylase 6 have hyperacetylated tubulin but are viable and develop normally', Molecular and Cellular Biology, vol. 28, no. 5, pp. 1688-1701. https://doi.org/10.1128/MCB.01154-06

Mice lacking histone deacetylase 6 have hyperacetylated tubulin but are viable and develop normally. / Zhang, Yu; Kwon, So Hee; Yamaguchi, Teppei; Cubizolles, Fabien; Rousseaux, Sophie; Kneissel, Michaela; Cao, Chun; Li, Na; Cheng, Hwei Ling; Chua, Katrin; Lombard, David; Mizeracki, Adam; Matthias, Gabriele; Alt, Frederick W.; Khochbin, Saadi; Matthias, Patrick.

In: Molecular and Cellular Biology, Vol. 28, No. 5, 03.2008, p. 1688-1701.

Research output: Contribution to journalArticle

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T1 - Mice lacking histone deacetylase 6 have hyperacetylated tubulin but are viable and develop normally

AU - Zhang, Yu

AU - Kwon, So Hee

AU - Yamaguchi, Teppei

AU - Cubizolles, Fabien

AU - Rousseaux, Sophie

AU - Kneissel, Michaela

AU - Cao, Chun

AU - Li, Na

AU - Cheng, Hwei Ling

AU - Chua, Katrin

AU - Lombard, David

AU - Mizeracki, Adam

AU - Matthias, Gabriele

AU - Alt, Frederick W.

AU - Khochbin, Saadi

AU - Matthias, Patrick

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