title: Oncomodulin, an EF-Hand Ca2+ Buffer, Is Critical for Maintaining Cochlear Function in Mice.
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.
  
  
  CONCLUSIONS
  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.
authors: Department of Otolaryngology, Washington University School of Medicine, St. Louis, Missouri 63110.
authors: Benton
authors: B
authors: Tong
authors: Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, California 90095, and.
authors: Aubrey J
authors: AJ
authors: Hornak
authors: Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, and Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts 02114.
authors: Stéphane F
authors: http://orcid.org/0000-0003-2813-6439
authors: SF
authors: Maison
authors: Department of Otolaryngology, Washington University School of Medicine, St. Louis, Missouri 63110.
authors: Kevin K
authors: KK
authors: Ohlemiller
authors: Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, and Department of Otology and Laryngology, Harvard Medical School, Boston, Massachusetts 02114.
authors: M Charles
authors: MC
authors: Liberman
authors: Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, California 90095, and dd.simmons@g.ucla.edu.
authors: Dwayne D
authors: http://orcid.org/0000-0002-1936-9508
authors: DD
authors: Simmons
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000172:deficiency / Q000502:physiology*; D003051:Cochlea / Q000502:physiology*; D020832:EF Hand Motifs / Q000502:physiology*; D006309:Hearing / Q000502:physiology*; D034381:Hearing Loss / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic
chemical_list: D002135:Calcium-Binding Proteins; C034733:oncomodulin; D002118:Calcium
keywords: calcium homeostasis; hearing loss; outer hair cell; parvalbumin