Inner ear dysfunction in caspase-3 deficient mice

Tomoko Makishima, Lara Hochman, Patrick Armstrong, Eric Rosenberger, Ryan Ridley, Minna Woo, Adrian Perachio, Scott Wood

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Background: Caspase-3 is one of the most downstream enzymes activated in the apoptotic pathway. In caspase-3 deficient mice, loss of cochlear hair cells and spiral ganglion cells coincide closely with hearing loss. In contrast with the auditory system, details of the vestibular phenotype have not been characterized. Here we report the vestibular phenotype and inner ear anatomy in the caspase-3 deficient (Casp3-/-) mouse strain.Results: Average ABR thresholds of Casp3-/- mice were significantly elevated (P < 0.05) compared to Casp3+/- mice and Casp3+/+ mice at 3 months of age. In DPOAE testing, distortion product 2F1-F2 was significantly decreased (P < 0.05) in Casp3-/- mice, whereas Casp3+/- and Casp3+/+ mice showed normal and comparable values to each other. Casp3-/- mice were hyperactive and exhibited circling behavior when excited. In lateral canal VOR testing, Casp3-/- mice had minimal response to any of the stimuli tested, whereas Casp3+/- mice had an intermediate response compared to Casp3+/+ mice. Inner ear anatomical and histological analysis revealed gross hypomorphism of the vestibular organs, in which the main site was the anterior semicircular canal. Hair cell numbers in the anterior- and lateral crista, and utricle were significantly smaller in Casp3-/- mice whereas the Casp3+/- and Casp3+/+ mice had normal hair cell numbers.Conclusions: These results indicate that caspase-3 is essential for correct functioning of the cochlea as well as normal development and function of the vestibule.

Original languageEnglish (US)
Article number102
JournalBMC Neuroscience
Volume12
DOIs
StatePublished - Oct 12 2011

ASJC Scopus subject areas

  • Neuroscience(all)
  • Cellular and Molecular Neuroscience

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    Makishima, T., Hochman, L., Armstrong, P., Rosenberger, E., Ridley, R., Woo, M., Perachio, A., & Wood, S. (2011). Inner ear dysfunction in caspase-3 deficient mice. BMC Neuroscience, 12, [102]. https://doi.org/10.1186/1471-2202-12-102