Vestibular defects in head-tilt mice result from mutations in<i>Nox3</i>, encoding an NADPH oxidase

TLDR

The vestibular system of the inner ear perceives motion and gravity through otoconia, tiny biomineral particles that deflect hair cell stereocilia in response to gravity or linear acceleration, transducing kinetic movements into sensorineural action potentials. The study investigates an allelic series of mutations at the head‑tilt locus that affect the NADPH oxidase 3 (Nox3) gene. By analyzing these mutations, the authors examined the role of Nox3 in otoconia morphogenesis. The results demonstrate that Nox3 is essential for otoconia formation, marking the first identification of a protein with a clear enzymatic function indispensable for this process.

Abstract

The vestibular system of the inner ear is responsible for the perception of motion and gravity. Key elements of this organ are otoconia, tiny biomineral particles in the utricle and the saccule. In response to gravity or linear acceleration, otoconia deflect the stereocilia of the hair cells, thus transducing kinetic movements into sensorineural action potentials. Here, we present an allelic series of mutations at the otoconia-deficient head tilt (het) locus, affecting the gene for NADPH oxidase 3 (Nox3). This series of mutations identifies for the first time a protein with a clear enzymatic function as indispensable for otoconia morphogenesis.