title: Inner ear dysfunction in caspase-3 deficient mice.
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.
authors: Department of Otolaryngology, University of Texas Medical Branch, Galveston, Texas, USA. tomakish@utmb.edu
authors: Tomoko
authors: T
authors: Makishima
authors: Lara
authors: L
authors: Hochman
authors: Patrick
authors: P
authors: Armstrong
authors: Eric
authors: E
authors: Rosenberger
authors: Ryan
authors: R
authors: Ridley
authors: Minna
authors: M
authors: Woo
authors: Adrian
authors: A
authors: Perachio
authors: Scott
authors: S
authors: Wood
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D053148:Caspase 3 / Q000172:deficiency* / Q000235:genetics; D004195:Disease Models, Animal; D007758:Ear, Inner / Q000201:enzymology* / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D015837:Vestibular Diseases / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology*; D014722:Vestibule, Labyrinth / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology
chemical_list: C505409:Casp3 protein, mouse; D053148:Caspase 3