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Sharpened cochlear tuning in a mouse with a genetically modified tectorial membrane

Abstract

Frequency tuning in the cochlea is determined by the passive mechanical properties of the basilar membrane and active feedback from the outer hair cells, sensory-effector cells that detect and amplify sound-induced basilar membrane motions. The sensory hair bundles of the outer hair cells are imbedded in the tectorial membrane, a sheet of extracellular matrix that overlies the cochlea's sensory epithelium. The tectorial membrane contains radially organized collagen fibrils that are imbedded in an unusual striated-sheet matrix formed by two glycoproteins, α-tectorin (Tecta) and β-tectorin (Tectb). In Tectb−/− mice the structure of the striated-sheet matrix is disrupted. Although these mice have a low-frequency hearing loss, basilar-membrane and neural tuning are both significantly enhanced in the high-frequency regions of the cochlea, with little loss in sensitivity. These findings can be attributed to a reduction in the acting mass of the tectorial membrane and reveal a new function for this structure in controlling interactions along the cochlea.

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Figure 1: Targeted deletion of exons 1–4 of Tectb.
Figure 2: Tectorial membrane morphology and composition in mature Tectb+/− and Tectb−/− mutant mice.
Figure 3: Fine structure of the tectorial membrane and hair bundles.
Figure 4: Electrical and mechanical recordings from the cochleae of wild-type (red) and Tectb−/− (blue) mice.
Figure 5: Neural and acoustical recordings from the cochleae of wild-type (red) and Tectb−/− (blue) mice.

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Acknowledgements

We thank J. Hartley for the design and construction of electronic apparatus and C. Petit (Institut Pasteur, Paris) for the gift of the antibody to otogelin. This work is supported by grants from the Wellcome Trust, the Medical Research Council, EuroHear and the Biotechnology and Biological Sciences Research Council.

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P.K.L. and G.P.R. made the mutant mice, R.J.G. and G.P.R. carried out the morphological analyses, V.A.L., A.N.L. and I.J.R. carried out the physiological analyses and I.J.R. and G.P.R. wrote the manuscript.

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Correspondence to Ian J Russell or Guy P Richardson.

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The authors declare no competing financial interests.

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Russell, I., Legan, P., Lukashkina, V. et al. Sharpened cochlear tuning in a mouse with a genetically modified tectorial membrane. Nat Neurosci 10, 215–223 (2007). https://doi.org/10.1038/nn1828

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