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A mouse model for human deafness DFNB22 reveals that hearing impairment is due to a loss of inner hair cell stimulation
journal contribution
posted on 2023-06-08, 14:10 authored by Andrei N Lukashkin, P Kevin Legan, Thomas D Weddell, Victoria A Lukashkina, Richard GoodyearRichard Goodyear, Lindsey J Welstead, Christine Petit, Ian J Russell, Guy RichardsonThe gene causative for the human nonsyndromic recessive form of deafness DFNB22 encodes otoancorin, a 120-kDa inner ear-specific protein that is expressed on the surface of the spiral limbus in the cochlea. Gene targeting in ES cells was used to create an EGFP knock-in, otoancorin KO (Otoa(EGFP/EGFP)) mouse. In the Otoa(EGFP/EGFP) mouse, the tectorial membrane (TM), a ribbon-like strip of ECM that is normally anchored by one edge to the spiral limbus and lies over the organ of Corti, retains its general form, and remains in close proximity to the organ of Corti, but is detached from the limbal surface. Measurements of cochlear microphonic potentials, distortion product otoacoustic emissions, and basilar membrane motion indicate that the TM remains functionally attached to the electromotile, sensorimotor outer hair cells of the organ of Corti, and that the amplification and frequency tuning of the basilar membrane responses to sounds are almost normal. The compound action potential masker tuning curves, a measure of the tuning of the sensory inner hair cells, are also sharply tuned, but the thresholds of the compound action potentials, a measure of inner hair cell sensitivity, are significantly elevated. These results indicate that the hearing loss in patients with Otoa mutations is caused by a defect in inner hair cell stimulation, and reveal the limbal attachment of the TM plays a critical role in this process
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Publication status
- Published
Journal
Proceedings of the National Academy of Sciences of the United States of AmericaISSN
1091-6490Publisher
National Academy of SciencesExternal DOI
Issue
47Volume
109Page range
19351-19356Department affiliated with
- Neuroscience Publications
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- No
Peer reviewed?
- Yes
Legacy Posted Date
2013-01-02Usage metrics
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