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ORIGINAL RESEARCH article

Front. Cell. Neurosci.

Sec. Cellular Neurophysiology

Tmprss3 is expressed in several cell types of the inner ear including type II but hardly in type I spiral ganglion neurons

Provisionally accepted
  • Department of Otolaryngology, University Hospital and Faculty of Medicine, University of Tübingen, Tübingen, Germany

The final, formatted version of the article will be published soon.

Mutations in the transmembrane serine protease 3 gene (TMPRSS3) cause non-syndromic hearing impairment, with congenital (DFNB10) or late childhood onset (DFNB8). In some reports, these patients were found to have lower speech comprehension scores with cochlear implants (CIs) compared to CI users with other etiologies. Since CIs electrically stimulate spiral ganglion neurons (SGNs) to activate the auditory pathway, TMPRSS3 deficiency was presumed to cause a dysfunction or degeneration of these cells, of which type I SGNs form the predominant group. Here, we revisited the expression pattern of Tmprss3 in the developing and mature mouse inner ear on mRNA level with quantitative few-cell PCR and RNAscope, and on protein level with immunohistochemistry with an anti-TMPRSS3 antibody validated on knock-out tissue. In the organ of Corti, we demonstrate expression of Tmprss3 in inner and outer hair cells, particularly in the stereocilia, and in pillar cells. Furthermore, expression of this gene in root cells of the lateral wall of the stria vascularis indicates a potential function in K+ recycling, and expression in the spiral limbus may be linked to the generation of the tectorial membrane. Within Rosenthal's canal, in immature tissue, Tmprss3 was diffusely expressed in all SGNs, but in the mature ear, in type I SGNs we found only minor mRNA amounts with qPCR, RNAscope, and no specific immunolabelling. In contrast, in type II SGNs Tmprss3 expression is enhanced during maturation. We hypothesize that the background levels of Tmprss3 expression in type I SGNs are not directly responsible for the vitality of these neurons, and that indirect effects, like signaling cascades dependent on TMPRSS3 in other cell types, are crucial for type I SGN function and survival.

Keywords: Organ of Corti, Inner hair cells, Outer hair cells, Stereocilia bundle, hearing impairment, cochlear implant, spiral limbus, extracellular serine protease

Received: 21 Aug 2025; Accepted: 27 Oct 2025.

Copyright: © 2025 Arora, Pifková, Deutschmann and Reisinger. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Ellen Reisinger, ellen.reisinger@uni-tuebingen.de

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