Project Description

Genetic Dissection of Loxhd1 in Mice

Pei Wang
Pei WangPhD
Katharine Miller
Katharine MillerPhD
Nicolas Grillet
Nicolas GrilletPhD
graphical abstract for the project showing selection for the gene via PCR

A graphical abstract showing the experimental sequence of the study. 

We identified LOXHD1/DFNB77 as a deafness gene in humans and mice, and we want to understand its function at the molecular level. 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. 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. Pei uses CRISPR/Cas9 genome editing to produce new mouse and Katharine uses her expertise in imaging to localize LOXHD1 protein at the highest resolution using electronic microscopy in the hair bundle.