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Sensorineural Hearing Loss and Mitochondrial Apoptosis of Cochlear Spiral Ganglion Neurons in Fibroblast Growth Factor 13 Knockout Mice

Deafness is known to occur in more than 400 syndromes and accounts for almost 30% of hereditary hearing loss. The molecular mechanisms underlying such syndromic deafness remain unclear. Furthermore, deafness has been a common feature in patients with three main syndromes, the BÖrjeson-Forssman-Lehma...

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Autores principales: Yu, Yulou, Yang, Jing, Luan, Feng, Gu, Guoqiang, Zhao, Ran, Wang, Qiong, Dong, Zishan, Tang, Junming, Wang, Wei, Sun, Jinpeng, Lv, Ping, Zhang, Hailin, Wang, Chuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242186/
https://www.ncbi.nlm.nih.gov/pubmed/34220452
http://dx.doi.org/10.3389/fncel.2021.658586
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author Yu, Yulou
Yang, Jing
Luan, Feng
Gu, Guoqiang
Zhao, Ran
Wang, Qiong
Dong, Zishan
Tang, Junming
Wang, Wei
Sun, Jinpeng
Lv, Ping
Zhang, Hailin
Wang, Chuan
author_facet Yu, Yulou
Yang, Jing
Luan, Feng
Gu, Guoqiang
Zhao, Ran
Wang, Qiong
Dong, Zishan
Tang, Junming
Wang, Wei
Sun, Jinpeng
Lv, Ping
Zhang, Hailin
Wang, Chuan
author_sort Yu, Yulou
collection PubMed
description Deafness is known to occur in more than 400 syndromes and accounts for almost 30% of hereditary hearing loss. The molecular mechanisms underlying such syndromic deafness remain unclear. Furthermore, deafness has been a common feature in patients with three main syndromes, the BÖrjeson-Forssman-Lehmann syndrome, Wildervanck syndrome, and Congenital Generalized Hirsutism, all of which are characterized by loss-of-function mutations in the Fgf13 gene. Whether the pathogenesis of deafness in these syndromes is associated with the Fgf13 mutation is not known. To elucidate its role in auditory function, we generated a mouse line with conditional knockout of the Fgf13 gene in the inner ear (Fgf13 cKO). FGF13 is expressed predominantly in the organ of Corti, spiral ganglion neurons (SGNs), stria vascularis, and the supporting cells. Conditional knockout of the gene in the inner ear led to sensorineural deafness with low amplitude and increased latency of wave I in the auditory brainstem response test but had a normal distortion product otoacoustic emission threshold. Fgf13 deficiency resulted in decreased SGN density from the apical to the basal region without significant morphological changes and those in the number of hair cells. TUNEL and caspase-3 immunocytochemistry assays showed that apoptotic cell death mediated the loss of SGNs. Further detection of apoptotic factors through qRT-PCR suggested the activation of the mitochondrial apoptotic pathway in SGNs. Together, this study reveals a novel role for Fgf13 in auditory function, and indicates that the gene could be a potential candidate for understanding deafness. These findings may provide new perspectives on the molecular mechanisms and novel therapeutic targets for treatment deafness.
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spelling pubmed-82421862021-07-01 Sensorineural Hearing Loss and Mitochondrial Apoptosis of Cochlear Spiral Ganglion Neurons in Fibroblast Growth Factor 13 Knockout Mice Yu, Yulou Yang, Jing Luan, Feng Gu, Guoqiang Zhao, Ran Wang, Qiong Dong, Zishan Tang, Junming Wang, Wei Sun, Jinpeng Lv, Ping Zhang, Hailin Wang, Chuan Front Cell Neurosci Neuroscience Deafness is known to occur in more than 400 syndromes and accounts for almost 30% of hereditary hearing loss. The molecular mechanisms underlying such syndromic deafness remain unclear. Furthermore, deafness has been a common feature in patients with three main syndromes, the BÖrjeson-Forssman-Lehmann syndrome, Wildervanck syndrome, and Congenital Generalized Hirsutism, all of which are characterized by loss-of-function mutations in the Fgf13 gene. Whether the pathogenesis of deafness in these syndromes is associated with the Fgf13 mutation is not known. To elucidate its role in auditory function, we generated a mouse line with conditional knockout of the Fgf13 gene in the inner ear (Fgf13 cKO). FGF13 is expressed predominantly in the organ of Corti, spiral ganglion neurons (SGNs), stria vascularis, and the supporting cells. Conditional knockout of the gene in the inner ear led to sensorineural deafness with low amplitude and increased latency of wave I in the auditory brainstem response test but had a normal distortion product otoacoustic emission threshold. Fgf13 deficiency resulted in decreased SGN density from the apical to the basal region without significant morphological changes and those in the number of hair cells. TUNEL and caspase-3 immunocytochemistry assays showed that apoptotic cell death mediated the loss of SGNs. Further detection of apoptotic factors through qRT-PCR suggested the activation of the mitochondrial apoptotic pathway in SGNs. Together, this study reveals a novel role for Fgf13 in auditory function, and indicates that the gene could be a potential candidate for understanding deafness. These findings may provide new perspectives on the molecular mechanisms and novel therapeutic targets for treatment deafness. Frontiers Media S.A. 2021-06-16 /pmc/articles/PMC8242186/ /pubmed/34220452 http://dx.doi.org/10.3389/fncel.2021.658586 Text en Copyright © 2021 Yu, Yang, Luan, Gu, Zhao, Wang, Dong, Tang, Wang, Sun, Lv, Zhang and Wang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Yu, Yulou
Yang, Jing
Luan, Feng
Gu, Guoqiang
Zhao, Ran
Wang, Qiong
Dong, Zishan
Tang, Junming
Wang, Wei
Sun, Jinpeng
Lv, Ping
Zhang, Hailin
Wang, Chuan
Sensorineural Hearing Loss and Mitochondrial Apoptosis of Cochlear Spiral Ganglion Neurons in Fibroblast Growth Factor 13 Knockout Mice
title Sensorineural Hearing Loss and Mitochondrial Apoptosis of Cochlear Spiral Ganglion Neurons in Fibroblast Growth Factor 13 Knockout Mice
title_full Sensorineural Hearing Loss and Mitochondrial Apoptosis of Cochlear Spiral Ganglion Neurons in Fibroblast Growth Factor 13 Knockout Mice
title_fullStr Sensorineural Hearing Loss and Mitochondrial Apoptosis of Cochlear Spiral Ganglion Neurons in Fibroblast Growth Factor 13 Knockout Mice
title_full_unstemmed Sensorineural Hearing Loss and Mitochondrial Apoptosis of Cochlear Spiral Ganglion Neurons in Fibroblast Growth Factor 13 Knockout Mice
title_short Sensorineural Hearing Loss and Mitochondrial Apoptosis of Cochlear Spiral Ganglion Neurons in Fibroblast Growth Factor 13 Knockout Mice
title_sort sensorineural hearing loss and mitochondrial apoptosis of cochlear spiral ganglion neurons in fibroblast growth factor 13 knockout mice
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242186/
https://www.ncbi.nlm.nih.gov/pubmed/34220452
http://dx.doi.org/10.3389/fncel.2021.658586
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