Functional cooperation between two otoconial proteins Oc90 and Nox3

Yinfang Xu, Liping Yang, Xing Zhao, Yan Zhang, Timothy A Jones, Sherri M. Jones, Yunxia Wang Lundberg

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Otoconia-related vertigo and balance deficits are common in humans, but the molecular etiology is unknown at present. OBJECTIVE: In order to study mechanisms of otoconia formation and maintenance, we have investigated whether otoconin-90 (Oc90), the predominant otoconial constituent protein, and the NADPH oxidase Nox3, an essential regulatory protein for otoconia formation, are functionally interlinked. METHODS: We performed balance behavioral, electrophysiological, morphological and molecular cellular analyses. RESULTS: Double heterozygous mutant mice for Oc90 and Nox3 show severe imbalance, albeit less profound than double null mutants. In contrast, single heterozygous mutant mice have normal balance. Double heterozygous mice have otoconia defects and double null mice have no otoconia. In addition, some hair bundles in the latter mice go through accelerated degeneration. In vitro calcification analysis in cells stably expressing these proteins singly and doubly shows much more intense calcification in the double transfectants. CONCLUSIONS: Oc90 and Nox3 augment each other's function, which is not only critical for otoconia formation but also for hair bundle maintenance.

Original languageEnglish (US)
Pages (from-to)441-449
Number of pages9
JournalJournal of Vestibular Research: Equilibrium and Orientation
Volume31
Issue number6
DOIs
StatePublished - 2021

Keywords

  • balance
  • calcification
  • hair bundle
  • Nox3
  • Oc90

ASJC Scopus subject areas

  • Neuroscience(all)
  • Otorhinolaryngology
  • Sensory Systems
  • Clinical Neurology

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