Wbp2 is required for normal glutamatergic synapses in the cochlea and is crucial for hearing
| Autor: | Buniello, Annalisa, Ingham, Neil J., Lewis, Morag A., Huma, Andreea C., Martinez-Vega, Raquel, Varela-Nieto, Isabel, Vizcay-Barrena, Gema, Fleck, Roland A., Houston, Oliver, Bardhan, Tanaya, Johnson, Stuart L., White, Jacqueline K., Yuan, Huijun, Marcotti, Walter, Steel, Karen P. |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: | |
| Zdroj: | Buniello, A, Ingham, N J, Lewis, M A, Huma, A C, Martinez-Vega, R, Varela-Nieto, I, Vizcay-Barrena, G, Fleck, R A, Houston, O, Bardhan, T, Johnson, S L, White, J K, Yuan, H, Marcotti, W & Steel, K P 2016, ' Wbp2 is required for normal glutamatergic synapses in the cochlea and is crucial for hearing ', EMBO Molecular Medicine, vol. 8, no. 3, pp. 191-207 . https://doi.org/10.15252/emmm.201505523 |
| DOI: | 10.15252/emmm.201505523 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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