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.
authors.affiliation: Department of Otolaryngology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX, 77555-0521, USA.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Armstrong
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Wood
authors.forename: Naoki
authors.initials: N
authors.lastname: Shimizu
authors.forename: Kael
authors.initials: K
authors.lastname: Kuster
authors.forename: Adrian
authors.initials: A
authors.lastname: Perachio
authors.forename: Tomoko
authors.initials: T
authors.lastname: Makishima
mesh_terms: D000054:Acceleration; D000704:Analysis of Variance; D000818:Animals; D053477:Apoptotic Protease-Activating Factor 1 / Q000235:genetics / Q000378:metabolism; D001696:Biomechanical Phenomena; D053148:Caspase 3 / Q000172:deficiency* / Q000235:genetics; D005260:Female; D019416:Head Movements / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009759:Nystagmus, Pathologic / Q000235:genetics* / Q000473:pathology*; D010037:Otolithic Membrane / Q000502:physiology*; D012027:Reflex, Vestibulo-Ocular / Q000235:genetics*; D012399:Rotation; D012665:Semicircular Canals / Q000503:physiopathology*; D014724:Vestibular Function Tests
chemical_list: C506593:Apaf1 protein, mouse; D053477:Apoptotic Protease-Activating Factor 1; C505409:Casp3 protein, mouse; D053148:Caspase 3
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