Deafness and Cochlear Fibrocyte Alterations in Mice Deficient for the Inner Ear Protein Otospiralin

Abstract

In the cochlea, the mammalian auditory organ, fibrocytes of the mesenchymal nonsensory regions play important roles in cochlear physiology, including the maintenance of ionic and hydric components in the endolymph. Occurrence of human deafness in fibrocyte alterations underlines their critical roles in auditory function. We recently described a novel gene, Otos, which encodes otospiralin, a small protein of unknown function that is produced by the fibrocytes of the cochlea and vestibule. We now have generated mice with deletion of Otos and found that they show moderate deafness, with no frequency predominance. Histopathology revealed a degeneration of type II and IV fibrocytes, while hair cells and stria vascularis appeared normal. Together, these findings suggest that impairment of fibrocytes caused by the loss in otospiralin leads to abnormal cochlear physiology and auditory function. This moderate dysfunction may predispose to age-related hearing loss.

ACKNOWLEDGMENTS

We thank Harold Cremer (CNRS UMR 6156, IBDM, Marseille, France) for providing ES cells and Marie-Christine Simmler (INSERM U. 587, Paris, France) for giving us the LacZneo cassette. Blastocyste injection and chimeras were obtained at the Plateforme de Recombinaison Homologue in the Cochin Institute (INSERM). Animals were bred by Mireille Gallego. SEM and TEM were performed at CRIC (Centre Régional d'Imagerie Cellulaire) with the technical support of Chantal Cazevieille and Florence Tribillac. We thank Jean-Louis Pasquier for artwork.

This study was supported by grants from the Institut de la Santé et de la Recherche Médicale (INSERM). B.D. has a fellowship from Caisse d'Epargne, Montpellier, and Région Languedoc-Roussillon, France.