Project Description

Characterization of the Hair Cell Mechanotransduction Defect in the Loxhd1 Mutant Mouse

Anthony Ricci
Anthony RicciPhD
Diletta Pozzi
Diletta PozziPhD
Nicolas Grillet
Nicolas GrilletPhD
graphical abstract showing LOXHD1 expression in mutant mouse

Mutant LOXHD1 hair cells do not have functional mechanotransduction pores.

A hair cell lights up as calcium flux is tracked. 

LOXHD1/DFNB77 is a deafness gene in humans and mice whose function at the molecular level is unknown and its identification the focus of this project. We recently found that LOXHD1 is required for the mechanotransduction process, the first step in the hearing process, but is unique in that it is required only after a week of normal function, and surprisingly, while located a distance from its site of action. Our collaborative approaches to this project use the cell physiology expertise of the Ricci lab to study functional changes in the mechanotransduction process in response to our genetic manipulations of LOXHD1. We use our genetic, molecular and optical expertise to generate models to be tested, to identify interacting partners and to assess the structural changes associated with these mutations.