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Preserved otolith organ function in caspase-3-deficient mice with impaired horizontal semicircular canal function

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Abstract

Genetically engineered mice are valuable models for elucidation of auditory and vestibular pathology. Our goal was to establish a comprehensive vestibular function testing system in mice using: (1) horizontal angular vestibulo-ocular reflex (hVOR) to evaluate semicircular canal function and (2) otolith-ocular reflex (OOR) to evaluate otolith organ function and to validate the system by characterizing mice with vestibular dysfunction. We used pseudo off-vertical axis rotation to induce an otolith-only stimulus using a custom-made centrifuge. For the OOR, horizontal slow-phase eye velocity and vertical eye position were evaluated as a function of acceleration. Using this system, we characterized hVOR and OOR in the caspase-3 (Casp3) mutant mice. Casp3 −/− mice had severely impaired hVOR gain, while Casp3 +/− mice had an intermediate response compared to WT mice. Evaluation of OOR revealed that at low-to-mid frequencies and stimulus intensity, Casp3 mutants and WT mice had similar responses. At higher frequencies and stimulus intensity, the Casp3 mutants displayed mildly reduced otolith organ-related responses. These findings suggest that the Casp3 gene is important for the proper function of the semicircular canals but less important for the otolith organ function.

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Acknowledgments

We thank J. Stahl (Case Western Reserve University) for discussions and review of the manuscript, and B. Lavery and J. Anderson for technical assistance and discussions of the project. Casp3 mutant mice were a gift from Dr. Minna Woo (University of Toronto). Apaf1 mutant mice were a gift from Dr. Tak Mak (University of Toronto). PA was supported by the Jeane B. Kempner fellowship. Research reported in this publication was supported by the National Institute on Deafness and Other Communication Disorders of the National Institutes of Health under Award Number K08DC011540 to TM. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Otolaryngology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX, 77555-0521, USA

    Patrick A. Armstrong, Scott J. Wood, Naoki Shimizu, Adrian Perachio & Tomoko Makishima

  2. School of Medicine, University of Texas Medical Branch, Galveston, TX, USA

    Patrick A. Armstrong & Kael Kuster

  3. Azusa Pacific University, Azusa, CA, USA

    Scott J. Wood

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  1. Patrick A. Armstrong
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Correspondence to Tomoko Makishima.

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Armstrong, P.A., Wood, S.J., Shimizu, N. et al. Preserved otolith organ function in caspase-3-deficient mice with impaired horizontal semicircular canal function. Exp Brain Res 233, 1825–1835 (2015). https://doi.org/10.1007/s00221-015-4254-4

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