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Article type: Research Article
Authors: Xu, Yinfanga | Yang, Lipinga; c | Zhao, Xinga | Zhang, Yana | Jones, Timothy A.b | Jones, Sherri M.b | Lundberg, Yunxia Wanga; *
Affiliations: [a] Vestibular Genetics Laboratory, Boys Town National Research Hospital, Omaha, NE, USA | [b] Department of Special Education and Communication Disorders, University of Nebraska-Lincoln, Lincoln, NE, USA | [c] Current address: Changsha Environmental Protection College, 10 Jinggui Rd, Yuhua Qu, Changsha, Hunan, China
Correspondence: [*] Corresponding author: Yunxia (Yesha) Wang Lundberg, Ph.D. Director, Vestibular Genetics Laboratory, Boys Town National Research Hospital, 555 N. 30th St. Omaha, NE 68131, USA. Tel.: +1 531 355 6735; Fax:+1 531 355 6351; E-mail: Yesha.Lundberg@boystown.org.
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.
Keywords: Oc90, Nox3, calcification, hair bundle, balance
DOI: 10.3233/VES-201591
Journal: Journal of Vestibular Research, vol. 31, no. 6, pp. 441-449, 2021
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