New insights into the role of pendrin (SLC26A4) in inner ear fluid homeostasis.

For over 100 years after the first description of the disorder, the molecular pathology underlying the deafness and thyroid pathology in Pendred syndrome (PS) remained unknown. In 1997, early progress towards understanding the molecular basis of the disorder was made when we identified the PS gene and found it to belong to the SLC26 family of anion transporters. The realization that an anion transporter was responsible for these clinical features soon highlighted a potential role for pendrin in thyroid hormone biosynthesis. The role of pendrin in deafness, however, remained unclear. Our determination of its expression pattern in the inner ear along with the development of a mouse with a targeted disruption of the Slc26a4 gene has revealed that Slc26a4 is expressed in areas of the endolymphatic compartment known to play a role in endolymph reabsorption and that absence of this protein leads to a profound prenatal endolymphatic hydrops and destruction of many of the epithelial cells surrounding the scala media. The precise mechanisms underlying endolymph reabsorption in the inner ear are not yet known; these studies, however, provide some of the groundwork for allowing the future delineation of these processes.