title: Wbp2 is required for normal glutamatergic synapses in the cochlea and is crucial for hearing.
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.
authors.affiliation: 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.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Buniello
authors.affiliation: Wolfson Centre For Age-Related Diseases, King's College London, London, UK Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Ingham
authors.affiliation: Wolfson Centre For Age-Related Diseases, King's College London, London, UK Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
authors.forename: Morag A
authors.initials: MA
authors.lastname: Lewis
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
authors.forename: Andreea C
authors.initials: AC
authors.lastname: Huma
authors.affiliation: 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.
authors.forename: Raquel
authors.initials: R
authors.lastname: Martinez-Vega
authors.affiliation: 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.
authors.forename: Isabel
authors.initials: I
authors.lastname: Varela-Nieto
authors.affiliation: Centre for Ultrastructural Imaging, King's College London, London, UK.
authors.forename: Gema
authors.initials: G
authors.lastname: Vizcay-Barrena
authors.affiliation: Centre for Ultrastructural Imaging, King's College London, London, UK.
authors.forename: Roland A
authors.initials: RA
authors.lastname: Fleck
authors.affiliation: Department of Biomedical Science, University of Sheffield, Sheffield, UK.
authors.forename: Oliver
authors.initials: O
authors.lastname: Houston
authors.affiliation: Department of Biomedical Science, University of Sheffield, Sheffield, UK.
authors.forename: Tanaya
authors.initials: T
authors.lastname: Bardhan
authors.affiliation: Department of Biomedical Science, University of Sheffield, Sheffield, UK.
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Johnson
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
authors.forename: Jacqueline K
authors.initials: JK
authors.lastname: White
authors.affiliation: Medical Genetics Center, Southwest Hospital Third Military Medical University, Chongqing, China.
authors.forename: Huijun
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Department of Biomedical Science, University of Sheffield, Sheffield, UK.
authors.forename: Walter
authors.initials: W
authors.lastname: Marcotti
authors.affiliation: 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.
authors.forename: Karen P
authors.initials: KP
authors.lastname: Steel
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D003051:Cochlea / Q000502:physiology*; D006309:Hearing; D034381:Hearing Loss / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans; D051379:Mice; D013569:Synapses / Q000502:physiology*; D015534:Trans-Activators
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015534:Trans-Activators; C106908:WBP2 protein, human
keywords: glutamate excitotoxicity; hearing impairment; hormonal signalling; ribbon synapses; transcriptional coactivator