Cross-species validation of a human age-related hearing loss candidate KLHDC7B as essential for mammalian hearing
Year: 2025
Type: article
Abstract: Although age-related hearing loss (ARHL) is the most common sensory loss in older adults, underlying mechanisms remain unclear. Recent genome-wide association studies (GWAS) linked variation in several genes with ARHL risk, including KLHDC7B , a gene of unknown function not previously linked to hearing. We demonstrate Klhdc7b is expressed exclusively in sensory hair cells in mouse cochlea. Utilizing two independent mouse knockout models ( Klhdc7b IMPC-/- and Klhdc7b Regn Δ/Δ ) we find that absence of Klhdc7b leads to severe early-onset, progressive hearing loss. Hair cells appear to develop normally, but outer hair cells are progressively lost from base-to-apex of the cochlea, a common pathology in ARHL. These results suggest KLHDC7B is required for maintenance rather than development, of auditory function. The validation in mouse of a human ARHL GWAS association suggests other novel candidates should be investigated. Our work provides two mouse models to study KLHDC7B function, and for development of therapeutic tools for ARHL.
Source: Communications Biology
Authors: Alexandra M. Kaufman, Benjamin Silver, Roberto A. Donnianni, Carlos Aguilar, Lingzi Niu, Daniel Johnson, Anwen Bullen, Alma Corona, Benjamin J. van Soldt, Nilay Vora, Gervasio Batista, Luz Cortes-Burgos, Jacqueline Copeland, Elika Fallah, Norman Zhang, Marina Lehmkuhl, Sarah Cancelarich, Kara Campos, Daniela Di Battista Miani, Jaylen Mumphrey, Susan D. Croll, Johnathon R. Walls, Mary Germino, Michael R. Bowl, Meghan C. Drummond, Sally J. Dawson
Language: English
Subfield: Sensory Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,190
Awards: G8384697097, G9000096260
OpenAlex ID: W4417435682