title: Tumor necrosis factor-alpha-mutant mice exhibit high frequency hearing loss.
abstract: Exogenous tumor necrosis factor-alpha (TNF-α) plays a role in auditory hair cell death by altering the expression of apoptosis-related genes in response to noxious stimuli. Little is known, however, about the function of TNF-α in normal hair cell physiology. We, therefore, investigated the cochlear morphology and auditory function of TNF-α-deficient mice. Auditory evoked brainstem response showed significantly higher thresholds, especially at higher frequencies, in 1-month-old TNF-α(-/-) mice as compared to TNF-α(+/-) and wild type (WT); hearing loss did not progress further from 1 to 4 months of age. There was no difference in the gross morphology of the organ of Corti, lateral wall, and spiral ganglion cells in TNF-α(-/-) mice compared to WT mice at 4 months of age, nor were there differences in the anatomy of the auditory ossicles. Outer hair cells were completely intact in surface preparations of the organ of Corti of TNF-α(-/-) mice, and synaptic ribbon counts of TNF-α(-/-) and WT mice at 4 months of age were similar. Reduced amplitudes of distortion product otoacoustic emissions, however, indicated dysfunction of outer hair cells in TNF-α(-/-) mice. Scanning electron microscopy revealed that stereocilia were sporadically absent in the basal turn and distorted in the middle turn. In summary, our results demonstrate that TNF-α-mutant mice exhibit early hearing loss, especially at higher frequencies, and that loss or malformation of the stereocilia of outer hair cells appears to be a contributing factor.
authors.affiliation: Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan, Ann Arbor, MI, 48109-5616, USA.
authors.forename: Naoki
authors.initials: N
authors.lastname: Oishi
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Zheng
authors.forename: Kayla
authors.initials: K
authors.lastname: Hill
authors.forename: Jochen
authors.initials: J
authors.lastname: Schacht
authors.forename: Su-Hua
authors.initials: SH
authors.lastname: Sha
mesh_terms: D000818:Animals; D003051:Cochlea / Q000473:pathology; D004429:Ear Ossicles / Q000473:pathology; D016057:Evoked Potentials, Auditory, Brain Stem; D018072:Hair Cells, Auditory, Outer / Q000473:pathology; D034381:Hearing Loss / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D009154:Mutation; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology*
chemical_list: D014409:Tumor Necrosis Factor-alpha