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EMBO Mol Med. 2016 Mar 1;8(3):191-207. doi: 10.15252/emmm.201505523.

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

Author information

1
Wolfson Centre For Age-Related Diseases, King's College London, London, UK Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK annalisa.buniello@kcl.ac.uk karen.steel@kcl.ac.uk.
2
Wolfson Centre For Age-Related Diseases, King's College London, London, UK Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
3
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
4
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, Madrid, Spain Centre for Biomedical Network Research on Rare Diseases (CIBERER), Unit 761, Instituto de Salud Carlos III, Madrid, Spain.
5
Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, Madrid, Spain Centre for Biomedical Network Research on Rare Diseases (CIBERER), Unit 761, Instituto de Salud Carlos III, Madrid, Spain.
6
Centre for Ultrastructural Imaging, King's College London, London, UK.
7
Department of Biomedical Science, University of Sheffield, Sheffield, UK.
8
Medical Genetics Center, Southwest Hospital Third Military Medical University, Chongqing, China.

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

PMID:
26881968
PMCID:
PMC4772953
DOI:
10.15252/emmm.201505523
[Indexed for MEDLINE]
Free PMC Article

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