CYLD deficiency causes auditory neuropathy due to reduced neurite outgrowth.
CYLD deficiency causes auditory neuropathy due to reduced neurite outgrowth.
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DOI：
10.1002/jcla.23783
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发表时间：
2021-06
影响因子：
2.7
通讯作者：
Li D
中科院分区：
文献类型：
--
作者：
Yang S;Ma N;Wu X;Ni H;Gao S;Sun L;Zhou P;Tala;Ran J;Zhou J;Liu M;Li D
听觉神经病变是听力损失的一个原因，已在许多动物模型中进行了研究。从毛细胞到螺旋神经节神经元的信号传输在正常听力中起着重要作用。 CYLD 是一种微管结合蛋白，脱泛素酶参与多种细胞过程的调节。在这项研究中，我们使用 Cyld 敲除 (KO) 小鼠和神经细胞系来检查 CYLD 是否与听神经病相关。使用 TDT RZ6 听觉生理学工作站研究 Cyld KO 小鼠的听力。通过 RT-PCR、免疫印迹和免疫荧光检查了 CYLD 在小鼠耳蜗和细胞系中的表达和定位。 SH-SY5Y 细胞中的 CYLD 表达被 shRNA 敲低，PC12 和 N2A 细胞中的 CYLD 表达被 siRNA 敲低。使用神经生长因子和视黄酸诱导神经突生长，并对敲除组和对照组之间神经突的出现和长度进行统计分析。 Cyld KO 小鼠有轻度听力障碍。此外，CYLD在小鼠耳蜗组织和不同神经细胞系中广泛表达。敲除 CYLD 显着减少了神经细胞生长的神经突的长度和比例。 Cyld KO小鼠的听力异常可能是由于耳蜗听觉神经细胞生长的神经突长度和数量减少所致，这表明CYLD是影响听力的关键蛋白。本研究的目的是探讨 CYLD 如何影响听力，在这里，我们发现 CYLD 损失会轻微损害小鼠的听力。通过细胞实验发现，CYLD表达的敲低会减少神经细胞中神经突的长度和比例，这可能是神经性听力障碍的潜在原因。
Auditory neuropathy is a cause of hearing loss that has been studied in a number of animal models. Signal transmission from hair cells to spiral ganglion neurons plays an important role in normal hearing. CYLD is a microtubule‐binding protein, and deubiquitinase involved in the regulation of various cellular processes. In this study, we used Cyld knockout (KO) mice and nerve cell lines to examine whether CYLD is associated with auditory neuropathy. Hearing of Cyld KO mice was studied using the TDT RZ6 auditory physiology workstation. The expression and localization of CYLD in mouse cochlea and cell lines were examined by RT‐PCR, immunoblotting, and immunofluorescence. CYLD expression was knocked down in SH‐SY5Y cells by shRNAs and in PC12 and N2A cells by siRNAs. Nerve growth factor and retinoic acid were used to induce neurite outgrowth, and the occurrence and length of neurites were statistically analyzed between knockdown and control groups. Cyld KO mice had mild hearing impairment. Moreover, CYLD was widely expressed in mouse cochlear tissues and different nerve cell lines. Knocking down CYLD significantly reduced the length and proportion of neurites growing from nerve cells. The abnormal hearing of Cyld KO mice might be caused by a decrease in the length and number of neurites growing from auditory nerve cells in the cochlea, suggesting that CYLD is a key protein affecting hearing. The purpose of this study was to explore how CYLD affects hearing, and here, we show that CYLD loss slightly impaired hearing in mice. Through cell experiments, it was found that knockdown of CYLD expression reduced the length and proportion of neurite in nerve cells, which may be the potential cause of neurological hearing impairment.
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DOI：
10.1056/nejmra1616601
发表时间：
2017-12-21
期刊：
The New England journal of medicine
影响因子：
--
作者：
Cunningham LL;Tucci DL
通讯作者：
Tucci DL
DOI：
10.26355/eurrev_202011_23791
发表时间：
2020-01-01
影响因子：
3.3
作者：
Han, Z.;Ding, J.;Chi, F-L
通讯作者：
Chi, F-L
DOI：
10.1523/jneurosci.2845-09.2009
发表时间：
2009-11-11
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kujawa SG;Liberman MC
通讯作者：
Liberman MC
影响因子：
2.7
作者：
Ma H;Luo X;Zhou P;He N;Zhou J;Liu M;Xie W
通讯作者：
Xie W
DOI：
10.1126/science.1241062
发表时间：
2014-05-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Géléoc GS;Holt JR
通讯作者：
Holt JR