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

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

Research output: Contribution to journalArticle

6 Scopus citations

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<sup>−/−</sup> mice had severely impaired hVOR gain, while Casp3<sup>+/−</sup> 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.

Original languageEnglish (US)
Pages (from-to)1825-1835
Number of pages11
JournalExperimental Brain Research
Volume233
Issue number6
DOIs
StatePublished - Apr 1 2015

Keywords

  • Caspase-3
  • Counter rotation
  • Mice
  • Otolith-ocular response
  • Pseudo off-vertical axis rotation
  • Vestibulo-ocular reflex

ASJC Scopus subject areas

  • Neuroscience(all)

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