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

Research output: Contribution to journalArticle

Annalisa Buniello, Neil J. Ingham, Morag A. Lewis, Andreea C. Huma, Raquel Martinez-Vega, Isabel Varela-Nieto, Gema Vizcay-Barrena, Roland A. Fleck, Oliver Houston, Tanaya Bardhan, Stuart L. Johnson, Jacqueline K. White, Huijun Yuan, Walter Marcotti, Karen P. Steel

Original languageEnglish
Pages (from-to)191-207
Number of pages17
JournalEMBO Molecular Medicine
Volume8
Issue number3
Early online date8 Feb 2016
DOIs
StateE-pub ahead of print - 8 Feb 2016

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  • Wbp2 is required for normal_BUNIELLO_Online 8Feb2016_GOLD VoR

    Wbp2_is_required_for_normal_BUNIELLO_Online_8Feb2016_GOLD_VoR.pdf, 4 MB, application/pdf

    8/07/2016

    Final published version

    CC BY

    This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

King's Authors

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. Synopsis: WBP2 was found to underlie deafness in mouse and patients. Wbp2-deficient mice were used as a genetic tool to gain insight into the functional link between hormonal signalling and hearing impairment. WBP2 mutations lead to deafness in mouse and humans. In the Wbp2-mutant mouse, the earliest abnormality is swelling of afferent nerve endings below inner hair cells and mice show progressive high-frequency hearing loss. Wbp2 deficiency leads to reduced expression of estrogen and progesterone receptors in the cochlea and disrupted expression of key post-synaptic proteins. WBP2 was found to underlie deafness in mouse and patients. Wbp2-deficient mice were used as a genetic tool to gain insight into the functional link between hormonal signalling and hearing impairment.

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