Wbp2 Is Novel Deafness Gene; Gene Product Acts on Estrogen Signaling Pathway in Cochlea; Findings Suggest New Targets for Possible Therapeutic Intervention in Progressive Hearing Loss

eRsearchers at King’s College London and the Wellcome Trust Sanger Institute in the UK have, for the first time, demonstrated a direct link between the mouse Wbp2 (WW domain-binding protein 2) gene and progressive hearing loss. The scientists report that the loss of Wbp2 expression leads to progressive high-frequency hearing loss in mice, as well as in two clinical cases of children with deafness with no other obvious features, except that each carried two different variants of the WBP2 gene, the human gene that corresponds to the mouse Wbp2 gene. The results were published on February 8, 2016 in EMBO Molecular Medicine. The open-access article is titled “Wbp2 Is Required for Normal Glutamatergic Synapses in the Cochlea and Is Crucial for Hearing.” The scientists have shown that the hearing impairment is linked to hormonal signaling rather than to hair cell degeneration. The human WBP2 protein acts as a transcriptional co-activator for the human estrogen receptor α (ESR1) and the human progesterone receptor (PGR). Similarly, the mouse Wbp2 protein is known as a transcriptional co-activator for mouse estrogen receptor Esr1 and mouse progesterone receptor Pgr. The loss of Wbp2 causes, not only progressive high-frequency hearing loss, but also results in reduced expression of Esr1, Esr2, and Pgr in the cochlea – a part of the inner ear. Understanding the estrogen-sensitive molecular networks specific to hearing offers an unprecedented putative new target for the control of the estrogen signaling pathway in the auditory system that might prevent, or even reverse, progressive hearing loss.
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