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

被引：37

作者：

Buniello, Annalisa ^{[1
,2
]}

Ingham, Neil J. ^{[1
,2
]}

Lewis, Morag A. ^{[1
,2
]}

Huma, Andreea C. ^{[2
]}

Martinez-Vega, Raquel ^{[2
,3
,4
]}

Varela-Nieto, Isabel ^{[3
,4
]}

Vizcay-Barrena, Gema ^{[5
]}

Fleck, Roland A. ^{[5
]}

Houston, Oliver

Bardhan, Tanaya ^{[6
]}

Johnson, Stuart L. ^{[6
]}

White, Jacqueline K. ^{[2
]}

Yuan, Huijun ^{[7
]}

Marcotti, Walter ^{[6
]}

Steel, Karen P. ^{[1
,2
]}

机构：

[1] Kings Coll London, Wolfson Ctr Age Related Dis, London WC2R 2LS, England

[2] Wellcome Trust Genome Campus, Wellcome Trust Sanger Inst, Hinxton, England

[3] CSIC UAM, Inst Invest Biomed Alberto Sols, Madrid, Spain

[4] Inst Salud Carlos III, Unit 761, Ctr Biomed Network Res Rare Dis CIBERER, Madrid, Spain

[5] Kings Coll London, Ctr Ultrastruct Imaging, London WC2R 2LS, England

[6] Univ Sheffield, Dept Biomed Sci, Sheffield S10 2TN, S Yorkshire, England

[7] Third Mil Med Univ, Southwest Hosp, Ctr Med Genet, Chongqing, Peoples R China

来源：

EMBO MOLECULAR MEDICINE | 2016年 / 8卷 / 03期

基金：

英国惠康基金; 英国生物技术与生命科学研究理事会;

关键词：

glutamate excitotoxicity; hearing impairment; hormonal signalling; ribbon synapses; transcriptional coactivator; ESTROGEN-RECEPTOR-BETA; LONG-TERM POTENTIATION; INNER-EAR; POSTMENOPAUSAL WOMEN; HAIR-CELLS; SYNAPTIC PLASTICITY; MAMMALIAN COCHLEA; PROTEIN MUTATIONS; STRIA VASCULARIS; AUDITORY-SYSTEM;

D O I：

10.15252/emmm.201505523

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

WBP2 encodes the WW domain-binding protein 2 that acts as a transcriptional coactivator for estrogen receptor (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.

引用

页码：191 / 207

页数：17

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