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.
Highlights
Progressive hearing loss is very common in the human population, but we know very little about its molecular basis and have no medical therapies
As we found no evidence of hair cell degeneration in the mouse Wbp2 mutants, we investigated the biophysical properties of inner hair cells (IHCs) in isolated organ of Corti preparations from young adult mouse mutants and littermate controls
This is a composite image made of several synapses taken from a single IHC from a single wt and a single hom, representing double labelling experiments performed on 3 mutants and 3 controls
Summary
Progressive hearing loss is very common in the human population, but we know very little about its molecular basis and have no medical therapies. IHCs have a specialised synapse with a pre-synaptic ribbon thought to gather synaptic vesicles to facilitate rapid release upon hair cell depolarisation. These ribbon synapses are innervated by the unbranched dendrites of spiral ganglion neurons, with a single ribbon synapse signalling to each afferent fibre, highlighting the importance of accurate neurotransmission at these synapses (Fuchs, 2005). The outer hair cells (OHCs) serve both as sensory receptors and as biological amplifiers Their sensory function is less well understood because their afferent innervation has small unmyelinated axons and constitutes only 5% of the cochlear nerve (Thiers et al, 2008). The molecular pathways underlying hair cell synaptic development and plasticity are still poorly understood
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