Wbp2 is required for normal glutamatergic synapses in the cochlea and is crucial for hearing

Abstract

Abstract WBP2 encodes the WW domain‐binding protein 2 that acts as a transcriptional coactivator for estrogen receptor α (ESR1) and progesterone receptor (PGR). We reported that the loss of Wbp2 expression leads to progressive high‐frequency hearing loss in mouse, as well as in two deaf children, each carrying two different variants in the WBP2 gene. The earliest abnormality we detect in Wbp2‐deficient mice is a primary defect at inner hair cell afferent synapses. This study defines a new gene involved in the molecular pathway linking hearing impairment to hormonal signalling and provides new therapeutic targets.

Keywords

• glutamate excitotoxicity
• hearing impairment
• hormonal signalling
• ribbon synapses
• transcriptional coactivator