AUTHOR=Ratzan Evan M. , Lee John , Madison Margot A. , Zhu Hong , Zhou Wu , Géléoc Gwenaëlle S. G. , Holt Jeffrey R. 

TITLE=TMC function, dysfunction, and restoration in mouse vestibular organs

JOURNAL=Frontiers in Neurology

VOLUME=Volume 15 - 2024

YEAR=2024

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2024.1356614

DOI=10.3389/fneur.2024.1356614

ISSN=1664-2295

ABSTRACT=Tmc1 and Tmc2 are essential pore-forming subunits of mechanosensory transduction channels
localized to the tips of stereovilli in auditory and vestibular hair cells of the inner ear. In vestibular
organs, Tmc1 and Tmc2 show dynamic developmental changes, differences in regional
expression patterns, and overall expression levels, which differ between the utricle and saccule.
These underlying changes contribute to unanticipated phenotypic loss of vestibular signaling in
Tmc1 KO mice, measured as vestibular sensory evoked potentials (VsEPs) and vestibulo-ocular
reflexes (VORs). In contrast, Tmc2 KO mice retain VsEPs despite the loss of the calcium
buffering protein calretinin, a characteristic biomarker of mature striolar calyx-only afferents. We
find neonatal Tmc1 gene replacement therapy is sufficient to restore linear VsEP in Tmc1 KO
mice for up to six months post-injection.