Endocochlear potential contributes to hair cell death in TMPRSS3 hearing loss.

ABSTRACT: Pathogenic variants in the gene TMPRSS3 are a common cause of hearing loss in humans, although the causal mechanisms remain unknown. Previous work has shown that Tmprss3Y260X/Y260X mice exhibit normal hair cell development, mechanosensory transduction, and spiral ganglion patterning, but experience rapid hair cell death from P12 to P14 at the onset of hearing. Here, we demonstrate that Tmprss3Y260X/Y260X mice display an early and temporary spike in endocochlear potential (EP) prior to the onset of hair cell death. In vitro experiments with cochlear explants from Tmprss3Y260X/Y260X mice and in vivo studies with Tmprss3Y260X/Y260X mice crossed with 2 different mutant models that lacked EP generation promoted hair cell survival. Furthermore, systemic administration of furosemide, a drug that

SUBMITTER: Shearer AE 

PROVIDER: S-EPMC12435832 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature