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

3 Citations (Scopus)

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

Fingerprint

Otolithic Membrane
Semicircular Canals
Vestibulo-Ocular Reflex
Reflex
Caspase 3
Mouse Casp3 protein
Pathology

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Preserved otolith organ function in caspase-3-deficient mice with impaired horizontal semicircular canal function. / Armstrong, Patrick A.; Wood, Scott J.; Shimizu, Naoki; Kuster, Kael; Perachio, Adrian; Makishima, Tomoko.

In: Experimental Brain Research, Vol. 233, No. 6, 01.04.2015, p. 1825-1835.

Research output: Contribution to journalArticle

Armstrong, Patrick A. ; Wood, Scott J. ; Shimizu, Naoki ; Kuster, Kael ; Perachio, Adrian ; Makishima, Tomoko. / Preserved otolith organ function in caspase-3-deficient mice with impaired horizontal semicircular canal function. In: Experimental Brain Research. 2015 ; Vol. 233, No. 6. pp. 1825-1835.
@article{38cf1438843c48a3a043710c637539e5,
title = "Preserved otolith organ function in caspase-3-deficient mice with impaired horizontal semicircular canal function",
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.",
keywords = "Caspase-3, Counter rotation, Mice, Otolith-ocular response, Pseudo off-vertical axis rotation, Vestibulo-ocular reflex",
author = "Armstrong, {Patrick A.} and Wood, {Scott J.} and Naoki Shimizu and Kael Kuster and Adrian Perachio and Tomoko Makishima",
year = "2015",
month = "4",
day = "1",
doi = "10.1007/s00221-015-4254-4",
language = "English (US)",
volume = "233",
pages = "1825--1835",
journal = "Experimental Brain Research",
issn = "0014-4819",
publisher = "Springer Verlag",
number = "6",

}

TY - JOUR

T1 - Preserved otolith organ function in caspase-3-deficient mice with impaired horizontal semicircular canal function

AU - Armstrong, Patrick A.

AU - Wood, Scott J.

AU - Shimizu, Naoki

AU - Kuster, Kael

AU - Perachio, Adrian

AU - Makishima, Tomoko

PY - 2015/4/1

Y1 - 2015/4/1

N2 - 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.

AB - 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.

KW - Caspase-3

KW - Counter rotation

KW - Mice

KW - Otolith-ocular response

KW - Pseudo off-vertical axis rotation

KW - Vestibulo-ocular reflex

UR - http://www.scopus.com/inward/record.url?scp=84929834255&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84929834255&partnerID=8YFLogxK

U2 - 10.1007/s00221-015-4254-4

DO - 10.1007/s00221-015-4254-4

M3 - Article

C2 - 25827332

AN - SCOPUS:84929834255

VL - 233

SP - 1825

EP - 1835

JO - Experimental Brain Research

JF - Experimental Brain Research

SN - 0014-4819

IS - 6

ER -