RGD Reference Report - Tumor Necrosis Factor-alpha-mutant Mice Exhibit High Frequency Hearing Loss. - Rat Genome Database

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Tumor Necrosis Factor-alpha-mutant Mice Exhibit High Frequency Hearing Loss.

Authors: Oishi, N  Chen, J  Zheng, HW  Hill, K  Schacht, J  Sha, SH 
Citation: Oishi N, etal., J Assoc Res Otolaryngol. 2013 Aug 31.
RGD ID: 7394699
Pubmed: (View Article at PubMed) PMID:23996384
DOI: Full-text: DOI:10.1007/s10162-013-0410-3

Exogenous tumor necrosis factor-alpha (TNF-alpha) 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-alpha in normal hair cell physiology. We, therefore, investigated the cochlear morphology and auditory function of TNF-alpha-deficient mice. Auditory evoked brainstem response showed significantly higher thresholds, especially at higher frequencies, in 1-month-old TNF-alpha-/- mice as compared to TNF-alpha+/- 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-alpha-/- 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-alpha-/- mice, and synaptic ribbon counts of TNF-alpha-/- 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-alpha-/- 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-alpha-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.

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Tnf  (tumor necrosis factor)

Genes (Mus musculus)
Tnf  (tumor necrosis factor)

Genes (Homo sapiens)
TNF  (tumor necrosis factor)

Additional Information