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The Journal of Neuroscience, October 4, 2006, 26(40):10188-10198; doi:10.1523/JNEUROSCI.2166-06.2006

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Cellular/Molecular
The Chloride Intracellular Channel Protein CLIC5 Is Expressed at High Levels in Hair Cell Stereocilia and Is Essential for Normal Inner Ear Function

Leona H. Gagnon,¹ Chantal M. Longo-Guess,¹ Mark Berryman,² Jung-Bum Shin,³ Katherine W. Saylor,¹ Heping Yu,¹ Peter G. Gillespie,³ and Kenneth R. Johnson¹

¹The Jackson Laboratory, Bar Harbor, Maine 04609, ²Ohio University College of Osteopathic Medicine, Athens, Ohio 45701, and ³Oregon Hearing Research Center and Vollum Institute, Portland, Oregon 97239

Correspondence should be addressed to Kenneth R. Johnson, The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609. Email: ken.johnson{at}jax.org

Although CLIC5 is a member of the chloride intracellular channel protein family, its association with actin-based cytoskeletal structures suggests that it may play an important role in their assembly or maintenance. Mice homozygous for a new spontaneous recessive mutation of the Clic5 gene, named jitterbug (jbg), exhibit impaired hearing and vestibular dysfunction. The jbg mutation is a 97 bp intragenic deletion that causes skipping of exon 5, which creates a translational frame shift and premature stop codon. Western blot and immunohistochemistry results confirmed the predicted absence of CLIC5 protein in tissues of jbg/jbg mutant mice. Histological analysis of mutant inner ears revealed dysmorphic stereocilia and progressive hair cell degeneration. In wild-type mice, CLIC5-specific immunofluorescence was detected in stereocilia of both cochlear and vestibular hair cells and also along the apical surface of Kolliker’s organ during cochlear development. Refined immunolocalization in rat and chicken vestibular hair cells showed that CLIC5 is limited to the basal region of the hair bundle, similar to the known location of radixin. Radixin immunostaining appeared reduced in hair bundles of jbg mutant mice. By mass spectrometry and immunoblotting, CLIC5 was shown to be expressed at high levels in stereocilia of the chicken utricle, in an approximate 1:1 molar ratio with radixin. These results suggest that CLIC5 associates with radixin in hair cell stereocilia and may help form or stabilize connections between the plasma membrane and the filamentous actin core.

Key words: CLIC5; mouse mutation; deafness; inner ear; hair cell; stereocilia

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Received May 22, 2006; revised July 25, 2006; accepted Aug. 20, 2006.

Correspondence should be addressed to Kenneth R. Johnson, The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609. Email: ken.johnson{at}jax.org

This article has been cited by other articles:

				A. Li, J. Xue, and E. H. Peterson Architecture of the Mouse Utricle: Macular Organization and Hair Bundle Heights J Neurophysiol, February 1, 2008; 99(2): 718 - 733. [Abstract] [Full Text] [PDF]

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