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

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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.

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Acknowledgements

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

Funding

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

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Authors and Affiliations

  1. Institute of Human Genetics, Jena University Hospital, Friedrich Schiller Universität, Am Klinikum 1, 07747, Jena, Germany

    Antje K. Huebner, Tanja Herrmann & Christian A. Hübner

  2. Department of Otolaryngology and Cluster of Excellence Hearing4all, Deutsches HörZentrum Hannover, Medical University Hannover, Karl-Wiechert-Allee 3, 30625, Hannover, Germany

    Hannes Maier

  3. Max-Delbrück Centrum für Molekulare Medizin (MDC) and NeuroCure, Robert-Rössle-Str. 10, 13092, Berlin, Germany

    Alena Maul

  4. Electron Microscopy Center, Jena University Hospital, Friedrich Schiller Universität, Ziegelmühlenweg 1, 07743, Jena, Germany

    Sandor Nietzsche

  5. Department of Biomedicine, Health, Aarhus University, Aarhus, Denmark

    Jeppe Praetorius

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  1. Antje K. Huebner
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  2. Hannes Maier
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  7. Christian A. Hübner
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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.

Corresponding author

Correspondence to Christian A. Hübner.

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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.

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The authors declare that they have no conflict of interest.

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Huebner, A.K., Maier, H., Maul, A. et al. Early Hearing Loss upon Disruption of Slc4a10 in C57BL/6 Mice. JARO 20, 233–245 (2019). https://doi.org/10.1007/s10162-019-00719-1

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