1. Genetics and Genomics
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Sensory transduction is required for normal development and maturation ofcochlear inner hair cell synapses

  1. John Lee
  2. Kosuke Kosuke Kawai
  3. Jeffrey R Holt  Is a corresponding author
  4. Gwenaelle Geleoc
  1. Boston Children's Hospital, United States
Research Article
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Cite this article as: eLife 2021;10:e69433 doi: 10.7554/eLife.69433


Acoustic overexposure and aging can damage auditory synapses in the inner ear by a process known as synaptopathy. These insults may also damage hair bundles and the sensory transduction apparatus in auditory hair cells. However, a connection between sensory transduction and synaptopathy has not been established. To evaluate potential contributions of sensory transduction to synapse formation and development, we assessed inner hair cell synapses in several genetic models of dysfunctional sensory transduction, including mice lacking Transmembrane Channel-like (Tmc) 1, Tmc2 or both, in Beethoven mice which carry a dominant Tmc1 mutation and in Spinner mice which carry a recessive mutation in Transmembrane inner ear (Tmie). Our analyses reveal loss of synapses in the absence of sensory transduction and preservation of synapses in Tmc1-null mice following restoration of sensory transduction via Tmc1 gene therapy. These results provide insight into the requirement of sensory transduction for hair cell synapse development and maturation.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Original raw data files have been uploaded to Dryad and are freely available here: https://doi.org/10.5061/dryad.fxpnvx0sb

The following data sets were generated

Article and author information

Author details

  1. John Lee

    FM Kirby Neurobiology Center, Boston Children's Hospital, Cambridge, United States
    Competing interests
    No competing interests declared.
  2. Kosuke Kosuke Kawai

    Boston Children's Hospital, Boston, United States
    Competing interests
    No competing interests declared.
  3. Jeffrey R Holt

    Boston Children's Hospital, Boston, United States
    For correspondence
    Competing interests
    Jeffrey R Holt, J.R.H holds a patent (62/638,697) on use of AAV9-PHP.B for gene therapy in the inner ear, is a scientific founder of Audition Therapeutics and an advisor to several biotech companies focused on inner ear therapeutics. The authors declare no other conflicts of interest..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7182-8011
  4. Gwenaelle Geleoc

    Boston Children's Hospital, Boston, United States
    Competing interests
    No competing interests declared.


NIDCD (RO1 DC013521)

  • Jeffrey R Holt

NIDCD (RO1 DC008853)

  • Gwenaelle Geleoc

NIDCD (F32 DC018233)

  • John Lee

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.


Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#20-02-4149R and #00001240) at Boston Children's Hospital.

Reviewing Editor

  1. Tobias Reichenbach, Friedrich-Alexander-University (FAU) Erlangen-Nürnberg, Germany

Publication history

  1. Received: April 15, 2021
  2. Accepted: November 1, 2021
  3. Accepted Manuscript published: November 4, 2021 (version 1)
  4. Version of Record published: November 17, 2021 (version 2)


© 2021, Lee et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.


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