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A deafness mutation isolates a second role for the tectorial membrane in hearing

Nature Neuroscience volume 8, pages 1035–1042 (2005)Cite this article

Abstract

α-tectorin (encoded by Tecta) is a component of the tectorial membrane, an extracellular matrix of the cochlea. In humans, the Y1870C missense mutation in TECTA causes a 50- to 80-dB hearing loss. In transgenic mice with the Y1870C mutation in Tecta, the tectorial membrane's matrix structure is disrupted, and its adhesion zone is reduced in thickness. These abnormalities do not seriously influence the tectorial membrane's known role in ensuring that cochlear feedback is optimal, because the sensitivity and frequency tuning of the mechanical responses of the cochlea are little changed. However, neural thresholds are elevated, neural tuning is broadened, and a sharp decrease in sensitivity is seen at the tip of the neural tuning curve. Thus, using TectaY1870C/+ mice, we have genetically isolated a second major role for the tectorial membrane in hearing: it enables the motion of the basilar membrane to optimally drive the inner hair cells at their best frequency.

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Figure 1: Targeted integration into the mouse Tecta gene.
Figure 2: Light microscopic analysis of TectaY1870C mice.
Figure 3: Ultrastructure of the tectorial membrane in TectaY1870C mice.
Figure 4: Hair bundle morphology in TectaY1870C mice.
Figure 5: Cochlear microphonics, basilar membrane tuning and DPOAEs in TectaY1870C mice.
Figure 6: Cochlear microphonics, CAPs and neural masking tuning curves in TectaY1870C mice.

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References

  1. Lim, D.J. Functional structure of the organ of Corti: a review. Hear. Res. 22, 117–146 (1986).

    Article  CAS  PubMed  Google Scholar 

  2. Brownell, W.E., Bader, C.R., Betrand, D. & de Ribaupierre, Y. Evoked mechanical responses of isolated cochlear outer hair cells. Science 227, 194–196 (1985).

    Article  CAS  PubMed  Google Scholar 

  3. Patuzzi, R.B., Yates, G.K. & Johnstone, B.M. Outer hair receptor currents and sensorineural hearing loss. Hear. Res. 42, 47–72 (1989).

    Article  CAS  PubMed  Google Scholar 

  4. Ruggero, M.A. & Rich, N.C. Furosemide alters organ of Corti mechanics: evidence for feedback of outer hair cells upon the basilar membrane. J. Neurosci. 11, 1057–1067 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kössl, M. & Russell, I.J. The phase and magnitude of hair cell receptor potentials and frequency tuning in the guinea pig cochlea. J. Neurosci. 12, 1575–1586 (1992).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Spoendlin, H. Anatomy of cochlear innervation. Am. J. Otolaryngol. 6, 453–467 (1985).

    Article  CAS  PubMed  Google Scholar 

  7. Kimura, R.S. Hairs of the cochlear sensory cells and their attachment to the tectorial membrane. Acta Otolaryngol. (Stockh.) 61, 55–72 (1966).

    Article  CAS  Google Scholar 

  8. Hasko, J.A. & Richardson, G.P. The ultrastructural organization and properties of the mouse tectorial membrane matrix. Hear. Res. 35, 21–38 (1988).

    Article  CAS  PubMed  Google Scholar 

  9. Richardson, G.P., Russell, I.J., Duance, V.C. & Bailey, A.J. Polypeptide composition of the mammalian tectorial membrane. Hear. Res. 25, 45–60 (1987).

    Article  CAS  PubMed  Google Scholar 

  10. Thalmann, I. et al. Composition and supramolecular organization of the tectorial membrane. Laryngoscope 97, 357–367 (1987).

    Article  CAS  PubMed  Google Scholar 

  11. Legan, P.K., Rau, A., Keen, J.N. & Richardson, G.P. The mouse tectorins: modular matrix proteins of the inner ear homologous to components of the sperm-egg adhesion system. J. Biol. Chem. 272, 8791–8801 (1997).

    Article  CAS  PubMed  Google Scholar 

  12. Cohen-Salmon, M., El-Amraoui, A., Leibovici, M. & Petit, C. Otogelin: a glycoprotein specific to the acellular membranes of the inner ear. Proc. Natl. Acad. Sci. USA 94, 14450–14455 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Verhoeven, K. et al. Mutations in human α-tectorin cause autosomal dominant non-syndromic hearing impairment. Nat. Genet. 19, 60–62 (1998).

    Article  CAS  PubMed  Google Scholar 

  14. Davis, H. Transmission and transduction in the cochlea. Laryngoscope 68, 359–382 (1957).

    Article  Google Scholar 

  15. Zwislocki, J.J. Theory of cochlear mechanics. Hear. Res. 2, 171–182 (1980).

    Article  CAS  PubMed  Google Scholar 

  16. Zwislocki, J.J. Analysis of cochlear mechanics. Hear. Res. 22, 155–169 (1986).

    Article  CAS  PubMed  Google Scholar 

  17. Allen, J.B. Cochlear micromechanics - a physical model of transduction. J. Acoust. Soc. Am. 68, 1660–1670 (1980).

    Article  CAS  PubMed  Google Scholar 

  18. Legan, P.K. et al. A targeted deletion in α-tectorin reveals the tectorial membrane is required for the gain and timing of cochlear feedback. Neuron 28, 273–285 (2000).

    Article  CAS  PubMed  Google Scholar 

  19. Gummer, A.W., Hemmert, W. & Zenner, H.P. Resonant tectorial membrane motion in the inner ear: Its crucial role in frequency tuning. Proc. Natl. Acad. Sci. USA 93, 8727–8732 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Hemmert, W., Zenner, H.P. & Gummer, A.W. Three-dimensional motion of the organ of Corti. Biophys. J. 78, 2285–2297 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Lukashkin, A.N., Lukashkina, V.A., Legan, P.K., Richardson, G.P. & Russell, I.J. Role of the tectorial membrane revealed by otoacoustic emissions recorded from wild-type and transgenic Tecta (deltaENT/deltaENT) mice. J. Neurophysiol. 91, 163–171 (2004).

    Article  PubMed  Google Scholar 

  22. Lin, T. & Guinan, J.J. Auditory-nerve-fiber responses to high-level clicks: Interference patterns indicate that excitation is due to the combination of multiple drives. J. Acoust. Soc. Am. 107, 2615–2630 (2000).

    Article  CAS  PubMed  Google Scholar 

  23. Dallos, P., Billone, M.C., Durrant, J.D., Wang, C. & Raynor, S. Cochlear inner and outer hair cells: functional differences. Science 177, 356–358 (1972).

    Article  CAS  PubMed  Google Scholar 

  24. Russell, I.J. & Sellick, P.M. Low-frequency characteristics of intracellularly recorded receptor potentials in guinea-pig cochlear hair cells. J. Physiol. (Lond.) 338, 179–206 (1983).

    Article  CAS  Google Scholar 

  25. Patuzzi, R.B. & Yates, G.K. The low-frequency response of inner hair cells in the guinea pig cochlea: implications for fluid coupling and resonance of the stereocilia. Hear. Res. 30, 83–98 (1987).

    Article  CAS  PubMed  Google Scholar 

  26. Aranyosi, A.J. & Freemann, D.M. Sound-induced motions of individual cochlear hair bundles. Biophys. J. 87, 3536–3546 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Russell, I.J., Kössl, M. & Murugasu, E. A comparison between tone-evoked voltage responses of hair cells and basilar membrane displacements recorded in the basal turn of the guinea pig cochlea. in Advances in Hearing Research (eds. Manley, G.A., Klump, G.M., Köppl, C., Fastl, H. & Oeckinghaus, H.) 125–135 (World Scientific, Singapore, 1995).

    Google Scholar 

  28. Narayan, S.S., Temchin, A.N., Recio, A. & Ruggero, M.A. Frequency tuning of basilar membrane and auditory nerve fibers in the same cochleae. Science 282, 1882–1884 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kletsky, E.J. & Zwislocki, J.J. CM tuning can be compatible with sharply tuned receptor potentials. Hear. Res. 2, 549–557 (1980).

    Article  CAS  PubMed  Google Scholar 

  30. Frolenkov, G.I., Belyantseva, I.A., Kurc, M., Mastroianni, M.A. & Kachar, B. Cochlear outer hair cell electromotility can provide force for both low and high intensity distortion product otoacoustic emissions. Hear. Res. 126, 67–74 (1998).

    Article  CAS  PubMed  Google Scholar 

  31. Lukashkin, A.N., Lukashkina, V.A. & Russell, I.J. One source for distortion product otoacoustic emissions generated by low- and high-level primaries. J. Acoust. Soc. Am. 111, 2740–2748 (2002).

    Article  PubMed  Google Scholar 

  32. Santos-Sacchi, J. Harmonics of outer hair cell motility. Biophys. J. 65, 2217–2227 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Lukashkin, A.N. & Russell, I.J. A descriptive model of the receptor potential nonlinearities generated by the hair cell mechanoelectrical transducer. J. Acoust. Soc. Am. 103, 973–980 (1998).

    Article  CAS  PubMed  Google Scholar 

  34. Mom, T., Telischi, F.F., Martin, G.K. & Lonsbury-Martin, B.L. Measuring the cochlear blood flow and distortion-product otoacoustic emissions during reversible cochlear ischemia: a rabbit model. Hear. Res. 133, 40–52 (1999).

    Article  CAS  PubMed  Google Scholar 

  35. Robertson, D. Horseradish peroxidase injection of physiologically characterized afferent and efferent neurones in the guinea pig spiral ganglion. Hear. Res. 15, 113–121 (1984).

    Article  CAS  PubMed  Google Scholar 

  36. Davis, H., Tasaki, I. & Goldstein, R. The peripheral origin of activity, with reference to the ear. Cold Spring Harb. Symp. Quant. Biol. 17, 143–154 (1952).

    Article  CAS  PubMed  Google Scholar 

  37. Sellick, P., Patuzzi, R. & Robertson, D. Primary afferent and cochlear nucleus contributions to extracellular potentials during tone-bursts. Hear. Res. 176, 42–58 (2003).

    Article  PubMed  Google Scholar 

  38. Dallos, P. & Cheatham, M.A. Compound action potential (AP) tuning curves. J. Acoust. Soc. Am. 59, 591–597 (1976).

    Article  CAS  PubMed  Google Scholar 

  39. Jovine, L., Qi, H., Williams, Z. & Wassarman, P.M. The ZP domain is a conserved module for polymerisation of extracellular proteins. Nat. Cell Biol. 4, 457–461 (2002).

    Article  CAS  PubMed  Google Scholar 

  40. Bork, P. & Sander, C. A large domain common to sperm receptors (Zp2 and Zp3) and TGF-beta type III receptor. FEBS Lett. 300, 237–240 (1992).

    Article  CAS  PubMed  Google Scholar 

  41. Wassarman, P.M., Jovine, L. & Litscher, E.S. A profile of fertilization in mammals. Nat. Cell Biol. 3, E59–E64 (2001).

    Article  CAS  PubMed  Google Scholar 

  42. Mustapha, M. et al. An alpha-tectorin gene defect causes a newly identified autosomal recessive form of sensorineural pre-lingual non-syndromic deafness, DFNB21. Hum. Mol. Genet. 8, 409–412 (1999).

    Article  CAS  PubMed  Google Scholar 

  43. Liberman, M.C. & Kiang, N.Y.-S. Acoustic trauma in cats. Acta Otolaryngol. Suppl. 358, 1–63 (1978).

    CAS  PubMed  Google Scholar 

  44. Robles, L. & Ruggero, M.A. Mechanics of the mammalian cochlea. Physiol. Rev. 81, 1305–1352 (2001).

    Article  CAS  PubMed  Google Scholar 

  45. Brookes, A.J., Stevenson, B.J., Porteous, D.J. & Dorin, J.R. A series of vectors that simplify mammalian gene targeting. Transgenic Res. 2, 238–244 (1993).

    Article  CAS  PubMed  Google Scholar 

  46. Malumbres, M., Mangues, R., Ferrer, N., Lu, S. & Pellicer, C. Isolation of high molecular weight DNA for reliable genotyping of transgenic mice. Biotechniques 22, 1114–1119 (1997).

    Article  CAS  PubMed  Google Scholar 

  47. Knipper, M. et al. Thyroid hormone-deficient period prior to the onset of hearing is associated with reduced levels of beta-tectorin protein in the tectorial membrane: implication for hearing loss. J. Biol. Chem. 276, 39046–39052 (2001).

    Article  CAS  PubMed  Google Scholar 

  48. Russell, I.J. & Kössl, M. Micromechanical responses to tones in the auditory fovea of the greater mustached bat's cochlea. J. Neurophysiol. 82, 676–686 (1999).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors would like to thank M. Mellado, M. Kössl and M. Drexl for their helpful criticisms of the manuscript and J. Hartley for expert technical assistance. Supported by grants from The Wellcome Trust, Defeating Deafness and the Fonds Wetenschappelijk Onderzoek – Flanders.

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Authors and Affiliations

  1. School of Life Sciences, University of Sussex, Falmer, Brighton, BN1 9QG, UK

    P Kevin Legan, Victoria A Lukashkina, Richard J Goodyear, Andrei N Lukashkin, Ian J Russell & Guy P Richardson

  2. Medical Genetics Centre, Dept. of Biomedical Sciences, University of Antwerp, Universiteitsplein 1, Antwerp, 2610, Belgium

    Kristien Verhoeven & Guy Van Camp

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Correspondence to Ian J Russell or Guy P Richardson.

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Legan, P., Lukashkina, V., Goodyear, R. et al. A deafness mutation isolates a second role for the tectorial membrane in hearing. Nat Neurosci 8, 1035–1042 (2005). https://doi.org/10.1038/nn1496

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