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J Neurosci. 2016 Feb 3;36(5):1631-5. doi: 10.1523/JNEUROSCI.3311-15.2016.

Oncomodulin, an EF-Hand Ca2+ Buffer, Is Critical for Maintaining Cochlear Function in Mice.

Author information

1
Department of Otolaryngology, Washington University School of Medicine, St. Louis, Missouri 63110.
2
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, California 90095, and.
3
Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, and Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts 02114.
4
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, California 90095, and dd.simmons@g.ucla.edu.

Abstract

Oncomodulin (Ocm), a member of the parvalbumin family of calcium binding proteins, is expressed predominantly by cochlear outer hair cells in subcellular regions associated with either mechanoelectric transduction or electromotility. Targeted deletion of Ocm caused progressive cochlear dysfunction. Although sound-evoked responses are normal at 1 month, by 4 months, mutants show only minimal distortion product otoacoustic emissions and 70-80 dB threshold shifts in auditory brainstem responses. Thus, Ocm is not critical for cochlear development but does play an essential role for cochlear function in the adult mouse.

SIGNIFICANCE STATEMENT:

Numerous proteins act as buffers, sensors, or pumps to control calcium levels in cochlear hair cells. In the inner ear, EF-hand calcium buffers may play a significant role in hair cell function but have been very difficult to study. Unlike other reports of genetic disruption of EF-hand calcium buffers, deletion of oncomodulin (Ocm), which is predominately found in outer hair cells, leads to a progressive hearing loss after 1 month, suggesting that Ocm critically protects hearing in the mature ear.

KEYWORDS:

calcium homeostasis; hearing loss; outer hair cell; parvalbumin

PMID:
26843644
PMCID:
PMC4737773
DOI:
10.1523/JNEUROSCI.3311-15.2016
[Indexed for MEDLINE]
Free PMC Article

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