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Early Hearing Loss upon Disruption of Slc4a10 in C57BL/6 Mice

  • Antje K. Huebner
  • Hannes Maier
  • Alena Maul
  • Sandor Nietzsche
  • Tanja Herrmann
  • Jeppe Praetorius
  • Christian A. HübnerEmail author
Research Article

Abstract

The unique composition of the endolymph with a high extracellular K+ concentration is essential for sensory transduction in the inner ear. It is secreted by a specialized epithelium, the stria vascularis, that is connected to the fibrocyte meshwork of the spiral ligament in the lateral wall of the cochlea via gap junctions. In this study, we show that in mice the expression of the bicarbonate transporter Slc4a10/Ncbe/Nbcn2 in spiral ligament fibrocytes starts shortly before hearing onset. Its disruption in a C57BL/6 background results in early onset progressive hearing loss. This hearing loss is characterized by a reduced endocochlear potential from hearing onset onward and progressive degeneration of outer hair cells. Notably, the expression of a related bicarbonate transporter, i.e., Slc4a7/Nbcn1, is also lost in spiral ligament fibrocytes of Slc4a10 knockout mice. The histological analysis of the spiral ligament of Slc4a10 knockout mice does not reveal overt fibrocyte loss as reported for Slc4a7 knockout mice. The ultrastructural analysis, however, shows mitochondrial alterations in fibrocytes of Slc4a10 knockout mice. Our data suggest that Slc4a10 and Slc4a7 are functionally related and essential for inner ear homeostasis.

Keywords

bicarbonate transport Slc4a10 Slc4a7 NCBE deafness fibrocyte pH 

Notes

Acknowledgements

We thank Cynthia Halvorson for the final editing of the manuscript.

Author Contributions

H.M, A.M., S.N., T.H.: performed experiments, analyzed data, and wrote the paper.

A.K..: performed experiments, analyzed data, and wrote the paper.

J.P.: provided material and wrote the paper.

C.A.H.: initiated the study, supervised experiments, and wrote the paper.

Funding

This study was funded by grants of the DFG to C.A.H. (HU 800/5-1 and HU 800/8-1).

Compliance with Ethical Standards

All experiments were approved by the responsible local institution (Landesamt für Lebensmittelsicherheit und Verbraucherschutz, Bad Langensalza and Niedersächsisches Landesamt für Verbraucherschutz und Lebensmittelsicherheit, Germany) and comply with the ARRIVE guidelines.

Competing Interests

The authors declare that they have no conflict of interest.

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Copyright information

© Association for Research in Otolaryngology 2019

Authors and Affiliations

  • Antje K. Huebner
    • 1
  • Hannes Maier
    • 2
  • Alena Maul
    • 3
  • Sandor Nietzsche
    • 4
  • Tanja Herrmann
    • 1
  • Jeppe Praetorius
    • 5
  • Christian A. Hübner
    • 1
    Email author
  1. 1.Institute of Human GeneticsJena University Hospital, Friedrich Schiller UniversitätJenaGermany
  2. 2.Department of Otolaryngology and Cluster of Excellence Hearing4all, Deutsches HörZentrum HannoverMedical University HannoverHannoverGermany
  3. 3.Max-Delbrück Centrum für Molekulare Medizin (MDC) and NeuroCureBerlinGermany
  4. 4.Electron Microscopy CenterJena University Hospital, Friedrich Schiller UniversitätJenaGermany
  5. 5.Department of Biomedicine, HealthAarhus UniversityAarhusDenmark

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