The progeroid g ene BubR1 regulates axon myelination and motor function

Chan Il Choi, Ki Hyun Yoo, Syed Mohammed Qasim Hussaini, Byeong Tak Jeon, John Welby, Haiyun Gan, Isobel A Scarisbrick, Zhiguo Zhang, Darren J Baker, Jan Van Deursen, Moses Rodriguez, Mi-Hyeon D Jang

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Myelination, the process by which oligodendrocytes form the myelin sheath around axons, is key to axonal signal transduction and related motor function in the central nervous system (CNS). Aging is characterized by degenerative changes in the myelin sheath, although the molecular underpinnings of normal and aberrant myelination remain incompletely understood. Here we report that axon myelination and related motor function are dependent on BubR1, a mitotic checkpoint protein that has been linked to progeroid phenotypes when expressed at low levels and healthy lifespan when overabundant. We found that oligodendrocyte progenitor cell proliferation and oligodendrocyte density is markedly reduced in mutant mice with low amounts of BubR1 (BubR1H/H mice), causing axonal hypomyelination in both brain and spinal cord. Expression of essential myelin-related genes such as MBP and PLP1 was significantly reduced in these tissues. Consistent with defective myelination, BubR1H/H mice exhibited various motor deficits, including impaired motor strength, coordination, and balance, irregular gait patterns and reduced locomotor activity. Collectively, these data suggest that BubR1 is a key determinant of oligodendrocyte production and function and provide a molecular entry point to understand age-related degenerative changes in axon myelination.

Original languageEnglish (US)
Pages (from-to)2667-2688
Number of pages22
JournalAging
Volume8
Issue number11
DOIs
StatePublished - 2016

Keywords

  • BubR1
  • Corpus callosum
  • Motor function
  • Myelination
  • Oligodendrocytes
  • Spinal cord

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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  • Cite this

    Choi, C. I., Yoo, K. H., Hussaini, S. M. Q., Jeon, B. T., Welby, J., Gan, H., Scarisbrick, I. A., Zhang, Z., Baker, D. J., Van Deursen, J., Rodriguez, M., & Jang, M-H. D. (2016). The progeroid g ene BubR1 regulates axon myelination and motor function. Aging, 8(11), 2667-2688. https://doi.org/10.18632/aging.101032