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Dystrophin expression in the hair cells of the cochlea

  • Published:
Journal of Neurocytology

Summary

Dystrophin is normally expressed in a number of tissues including muscle, brain and the outer plexiform layer of the retina. In Duchenne and Becker muscular dystrophy abnormal or deficient dystrophin expression leads to muscle degeneration and has been implicated in mental retardation and a form of night blindness. We have examined the expression of dystrophin immunoreactivity in cochlear tissues of normal guinea-pig and mouse, and whether expression is perturbed in the cochlea of the dystrophic MDX mouse. A single band of approximately 427 kDa, corresponding to a full-length isoform of dystrophin was detected in guinea-pig and normal mouse but was absent from the MDX mouse. Cochleae from guinea-pig, normal and MDX mouse also showed a second dystrophin isoform of 116 kDa molecular weight with the C-terminal specific antibody. Immunostained guinea pig cochlear half turns were examined by laser scanning confocal microscopy. Dystrophin was localized in both inner and outer hair cells with staining patterns which were qualitatively similar with both antibodies. In the outer hair cells labelling of the lateral wall was especially distinctive. The synaptic region of both hair cell types was also strongly labelled.

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References

  • Ahn, A. H. &Kunkel, L. M. (1993) The structure and functional diversity of dystrophin.Nature Genetics 3, 283–91.

    PubMed  Google Scholar 

  • Angelborg, C. &Engstrom, H. (1973) The normal organ of Corti. InBasic Mechanisms of Hearing (edited byMoller, A. R.) pp. 125–82. New York, London: Academic Press.

    Google Scholar 

  • Bannister, L. H., Dodson, H. C., Astbury, A. F. &Douek, E. E. (1988) The cortical lattice: a highly ordered system of subsurface filaments in guinea-pig cochlear hair cells.Progress in Brain Research 74, 213–19.

    PubMed  Google Scholar 

  • Brown, S. C. &Dickson, G. (1994) Duchenne muscular dystrophy. InFrom Genetics to Gene Therapy (edited byLatchman, D. S.) pp. 45–70. Oxford: Bios Scientific Publishers.

    Google Scholar 

  • Brown, A. M., Mcdowell, B. &Forge, A. (1989) Acoustic distortion products can be used to monitor the effects of chronic gentamicin treatment.Hearing Research 42, 143–56.

    PubMed  Google Scholar 

  • Brownell, W. E., Bader, C. R., Bertrand, D. &DE Ribeaupierre, Y. (1985) Evoked mechanical responses of isolated outer hair cells.Science 227, 194–6.

    PubMed  Google Scholar 

  • Brundin, L., Flock, A. &Canlon, B. (1989) Soundinduced motility of isolated outer hair cels is frequency-specific.Nature 342, 814–16.

    PubMed  Google Scholar 

  • Bulfield, G., Siller, W. G., Wight, P. A. L. &Moore, K. J. (1984) X-Chromosome-linked muscluar dystrophy in the mouse.Proceedings of the National Academy of Sciences (USA)81, 1189–92.

    Google Scholar 

  • Byers, T. J., Kunkel, L. M. &Watkins, S. C. (1991) The subcellular distribution of dystrophin in mouse skeletal, cardiac and smooth muscle.Journal of Cell Biology 115, 411–21.

    PubMed  Google Scholar 

  • Byers, T. J., Lidov, H. G. W. &Kunkel, L. M. (1993) An alternative dystrophin transcript specific to peripheral nerve.Nature Genetics 4, 77–81.

    PubMed  Google Scholar 

  • Dulon, D., Zajic, G. &Schacht, J. (1990) Increasing intracellular free calcium induces circumferential contractions in isolated cochlear hair cells.Journal of Neuroscience 10, 1388–97.

    PubMed  Google Scholar 

  • England, S. B., Nicholson, L. V. B., Johnson, M. A., Forrest, S. M., Love, D. R., Zubrzycka-Gaarn, E. E., Bulman, D. E., Harris, J. B. &Davies, K. E. (1990) Very mild muscular dystrophy associated with deletion of 46% of dystrophin.Nature 343, 180–2.

    PubMed  Google Scholar 

  • Ervasti, J. M. &Campbell, K. P. (1991) Membrane organization of the dystrophin-glycoprotein complex.Cell 66, 1121–31.

    PubMed  Google Scholar 

  • Feener, C. A., Koenig, M. &Kunkel, L. M. (1989) Alternative splicing of human dystrophin mRNA generates isoforms at the carboxy terminus.Nature 338, 509–11.

    PubMed  Google Scholar 

  • Flock, A., Flock, B. &Ulfendahl, M. (1986) Mechanism of movement in outer hair cells and possible structural basis.Archives of Otorhinolaryngology 243, 83–90.

    Google Scholar 

  • Fong, P., Turner, P. R., Denetclaw, W. F. &Steinhardt, R. A. (1990) Increased activity of calcium leak channels in myotubes of Duchenne human and mdx mouse origin.Science 250, 673–5.

    PubMed  Google Scholar 

  • Forge, A., Zajic, G., Li, L., Nevill, G. &Schacht, J. (1993) Structural variability of the sub-surface cisternae in intact, isolated outer harr cells shown by fluorescent labelling of intracellular membranes and freeze-fracture.Hearing Research 64, 175–83.

    PubMed  Google Scholar 

  • Guilford, D. P., Ben-Arab, S., Blanchard, S., Levilliersm J., Weissenbach, J., Belkahia, A. &Petit, C. (1994) A non-syndrome form of neurosensory, recessive deafness maps to the pericentric region of chromosome 13q.Nature Genetics 6(1), 24–8.

    PubMed  Google Scholar 

  • Holley, M. C. &Ashmore, J. F. (1988) A cytoskeletal spring in cochlear outer hair cells.Nature 335, 635–7.

    PubMed  Google Scholar 

  • Holley, M. C. &Ashmore, J. F. (1990) Spectrin, actin and the structure of the cortical lattice in mammalian cochlear outer hair cells.Journal of Cell Science 96, 283–91.

    PubMed  Google Scholar 

  • Karlsson, K. K. &Flock, A. (1991) Quinine causes isolated outer hair cells to change length.Neuroscience Letters 116, 101–5.

    Google Scholar 

  • Kemp, D. T. (1978) Stimulated acoustic emisssons from within the human auditory system.Journal of the Acoustical Society of America 65, 1386–91.

    Google Scholar 

  • Kim, T-W., Wu, K., Xu, J-L &Black I. B. (1992) Detection of dystrophin in the postsynaptic density of rat brain and deficiency in a mouse model of Duchenne muscular dystrophy.Proceeding of the National Academy of Sciences (USA) 89, 11642–4.

    Google Scholar 

  • Kunkel, L. M. &Huffman, E. P. (1989) Duchenne/Becker muscular dystrophy: an overview of the gene, the protein and current diagnosis.British Medical Bulletin 45, 630–43.

    PubMed  Google Scholar 

  • Lalwani, A. K., Brister, J. R., Fex, J., Grundfast, K. M., Pikus, A. T., Ploplis, B., San-Agustin, T., Sharka, H. &Wilcox, E. R. (1994) A new nonsyndromic x-linked sensorineural hearing impairment linked to Xp21.2.American Journal of Human Genetics 55, 685–94.

    PubMed  Google Scholar 

  • Lansman, J. B. &Franco, A. J. (1991) What does dystrophin do in normal muscle?Journal of Muscle Research and Cell Motility 12, 409–11.

    PubMed  Google Scholar 

  • Lepage, E. L. (1989) Functional role of the olivocohlear bundle: a motor unit control system in the mammalian cochlea.Hearing Research 38, 177–98.

    PubMed  Google Scholar 

  • Lidov, H. G. W., Byers, T. J. &Kunkel, L. M. (1993) The distribution of dystrophin in the murine central nervous system: an immunocytochemical study.Neuroscience 54, 167–87.

    PubMed  Google Scholar 

  • Lidov, H. G. W., Byers T. J., Watkins, S. C. &Kunkel, L. M. (1990) Localization of dystrophin to postsynaptic regions of central nervous system cortical neurons.Nature 348, 725–8.

    PubMed  Google Scholar 

  • Man, N. T., Ellis, J., Love, D., Davies, K. E., Dickson, G. &Morris G. E. (1991) Localisation of the DMDL-geneencoded dystrophin-related protein using a panel of nineteen monoclonal antibodies.Journal of Cell Biology 115, 1695–700.

    PubMed  Google Scholar 

  • Nicholson, L. V. B., Davison, K., Falkous, G., Harwood, C., O'donnell, E., Slater, C. &Harris, J. B. (1989) Dystrophin in skeletal muscle: Western blot analysis using a monoclonal antibody.Journal of the Neurological Sciences 94, 125–36.

    PubMed  Google Scholar 

  • Petrof, B. J., Shrager, J. B., Hansell, H. S., Kelly, A. M. &Sweeney, H. L. (1993) Dystrophin protects the sarcolemma from stresses developed during muscle contraction.Proceedings of the National Academy of Sciences (USA) 90, 3710–14.

    Google Scholar 

  • Pillers, D'-A. M., Bulman, D. E., Weleber, R. G., Sigesmund, D. A., Musarella, M. A., Powell, B. R., Murphey, W. H., Westall, C., Panton, C., Becker L. E., Worton, R. G. &Ray, P. N. (1993) Dystrophin expression in the human retina is required for normal function as defined by electroretinography.Nature Genetics 4, 82–6.

    PubMed  Google Scholar 

  • Ruggero, M. A., &Rich, N. C. (1991) Furosemide alters organ of Corti mechanics: evidence for feedback of outer hair cells upon the basilar membrane.Journal of Neuroscience 11, 1057–67.

    PubMed  Google Scholar 

  • Schmitz, F., Holbach, M. &Dreckhahn, D. (1993) Colocalization of retinal dystrophin and actin in postsynaptic dendrites of rod and cone photoreceptor synapses.Histochemistry 100, 473–9.

    PubMed  Google Scholar 

  • Schofield, J. N., Blake, D. J., Simmons, C., Morris, G. E., Tinsley, J. M., Davies, K. E. &Edwards, Y. E. (1994) Apodystrophin-1 and apodystrophin-2, products of the Duchenne muscular dystrophy locus: expression during mouse embryogenesis and in cultured cell lines.Human Molecular Genetics 3, 1309–16.

    PubMed  Google Scholar 

  • Sealock, R. &Froehner, S. C. (1994) Dystrophinassociated proteins and synapse formation: α-dystroglycan the agrin receptor?Cell 77, 617–19.

    PubMed  Google Scholar 

  • Slepecky, N. B. (1989) Cytoplasmic actin and cochlear outer hair cell motility.Cell Tissue Research 257, 69–75.

    PubMed  Google Scholar 

  • Slepecky, N. B. &Ulfendahl, M. (1992) Actin-binding and microtubule-associated proteins in the organ of Corti.Hearing Research 57, 201–15.

    PubMed  Google Scholar 

  • Slepecky, N. B. &Ulfendahl, M. (1993) Evidence for calcium-binding proteins and calcium-dependent regulatory proteins in sensory cells of the organ of Corti.Hearing Research 70, 73–4.

    PubMed  Google Scholar 

  • Tinsley, J. M., Blake, D. J. &Davies, K. E. (1993) Apodystrophin-3: a 2.2kb transcript from the DMD locus encoding the dystrophin glycoprotein binding site site.Human Molecular Genetics 2 521–4.

    PubMed  Google Scholar 

  • Turner, P. R., Fong, P. Y., Denetclaw, W. F. &Steinhardt, R. A. (1991) Increased calcium influx in dystrophic muscle.Journal of Cell Biology 115 1701–12.

    PubMed  Google Scholar 

  • Uchino, M., Yoshioka, K., Miike, T., Tokunaga, M., Uyama, E., Teramoto, H., Naoe, H. &Ando, M. (1994a) Dystrophin and dystrophin-related protein in the brains of normal and mdx mice.Muscle and Nerve 17, 533–8.

    PubMed  Google Scholar 

  • Uchino, M., Teramoto, H., Naoes, H., Yoshioka, K., Miike, T. &Ando, M. (1994b) Localization and characterization of dystrophin in the central nervous system of controls and patients with Duchenne muscular dystrophy.Journal of Neurology Neurosurgery and Psychiatry 57, 426–9.

    Google Scholar 

  • Ulfendahl, M., Khanna, S. M. &Flock, A. (1989) Effects of caffeine on the micromechanics of the isolated cochlea.Acta Otolaryngology Supplement 467, 221–8.

    Google Scholar 

  • Way, M., Pope, B., Cross, R. A., Kendrick-Jones, J. &Weeds, A. G. (1992) Expression of the N-terminal domain of dystrophin inE. coli and demonstration of binding to F-actin.FEBS Letters 301, 243–5.

    PubMed  Google Scholar 

  • Wells, D. J., Wells, K. E., Walsh, F. S., Davies, K. E., Goldspink, G., Love, D. R., Chan-Thomas, P., Dunckley, M. G., Piper, T. &Dickson, G. (1992) Human dystrophin expression corrects the myopathie phenotype in transgenic mdx mice.Human Molecular Genetics 1, 35–40.

    PubMed  Google Scholar 

  • Ylikoski, J., Pirvola, U. &Lehtonen, E. (1992) Distribution of F-actin and fodrin in the hair cells of the guinea-pig cochlea as revealed by confocal fluoresence microscopy.Hearing Research 60, 80–8.

    PubMed  Google Scholar 

  • Zenner, H. P. (1986) Motile responses in outer hair cells.Hearing Research 22, 83–90.

    PubMed  Google Scholar 

  • Zurek, P. M., Clark, W. W. &Kim, D. O. (1981) The behaviour of acoustic distortion products in the ear canals of chinchillas with normal or damaged ears.Journal of the Acoustical Society of America 72, 774–80.

    Google Scholar 

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Authors and Affiliations

  1. Institute of Laryngology and Otology, University College London, 330/332, Gray's Inn Road, WC1X 8EE, London

    Hilary C. Dodson

  2. Division of Anatomy and Cell Biology, UMDS, Guy's Hospital, SE1 9RT, London

    Hilary C. Dodson

  3. Department of Biochemistry, Royal Holloway College, University of London, TW20 0EX, Egham, Surrey

    Tony A. Piper & George Dickson

  4. Department of Anatomy and Developmental Biology, University College London, Windeyer Building, Cleveland Street, W1P 6DB, London

    Jonathan D. W. Clarke

  5. Marjorie Crowe Neuromuscular Clinic, Newcomen Centre, Guy's Hospital, SE1 9RT, London, UK

    Rosalind M. Quinlivan

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  1. Hilary C. Dodson
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  2. Tony A. Piper
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  3. Jonathan D. W. Clarke
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  4. Rosalind M. Quinlivan
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  5. George Dickson
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Dodson, H.C., Piper, T.A., Clarke, J.D.W. et al. Dystrophin expression in the hair cells of the cochlea. J Neurocytol 24, 625–632 (1995). https://doi.org/10.1007/BF01257377

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  • DOI: https://doi.org/10.1007/BF01257377

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