Connexin30-Deficiency Causes Mild Hearing Loss With the Reduction of Endocochlear Potential and ATP Release.
Connexin30-Deficiency Causes Mild Hearing Loss With the Reduction of Endocochlear Potential and ATP Release.
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Connexin30 缺乏会导致轻度听力损失，并导致耳蜗电位和 ATP 释放减少
DOI：
10.3389/fncel.2021.819194
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发表时间：
2021
影响因子：
5.3
通讯作者：
Yang J
中科院分区：
文献类型：
--
作者：
Chen J;Chen P;He B;Gong T;Li Y;Zhang J;Lv J;Mammano F;Hou S;Yang J
GJB 2和GJB 6分别是编码连接蛋白26（Cx 26）和连接蛋白30（Cx 30）的相邻基因，在内耳中具有重叠表达。这两个基因都与最常见的单基因听力障碍，隐性孤立性耳聋DFNB 1有关。Cx 26在听觉发育中起重要作用，而Cx 30在听觉中的作用仍存在争议。先前的研究发现，Cx 30基因敲除小鼠有严重的听力损失，沿着的是Cx 26减少了90%，而另一种Cx 30基因敲除小鼠模型显示听力正常，Cx 26保留了近一半。在这项研究中，我们使用CRISPR/Cas9技术建立了一种新的Cx 30敲除小鼠模型（Cx 30 −/−），该模型保留了大约70%的Cx 26。我们发现，1、3和6个月大的Cx 30 −/−小鼠在全频率下表现出轻度听力损失。免疫荧光和HE染色表明Cx 30 −/−小鼠和野生型小鼠之间的耳蜗微结构没有显著差异。然而，透射电子显微镜显示Cx 30 −/−小鼠的血管纹中有轻微的空洞样损伤。Cx 30缺陷可导致耳蜗内电位（EP）的产生和ATP的释放减少，从而导致听力损失。总之，这项研究表明，缺乏Cx 30可导致听力损失，在本Cx 30敲除模型中Cx 26减少约30%。因此，Cx 30可能在听力发育中发挥重要而非多余的作用。
GJB2 and GJB6 are adjacent genes encoding connexin 26 (Cx26) and connexin 30 (Cx30), respectively, with overlapping expressions in the inner ear. Both genes are associated with the commonest monogenic hearing disorder, recessive isolated deafness DFNB1. Cx26 plays an important role in auditory development, while the role of Cx30 in hearing remains controversial. Previous studies found that Cx30 knockout mice had severe hearing loss along with a 90% reduction in Cx26, while another Cx30 knockout mouse model showed normal hearing with nearly half of Cx26 preserved. In this study, we used CRISPR/Cas9 technology to establish a new Cx30 knockout mouse model (Cx30−/−), which preserves approximately 70% of Cx26. We found that the 1, 3, and 6-month-old Cx30−/− mice showed mild hearing loss at full frequency. Immunofluorescence and HE staining suggested no significant differences in microstructure of the cochlea between Cx30−/− mice and wild-type mice. However, transmission electron microscopy showed slight cavity-like damage in the stria vascularis of Cx30−/− mice. And Cx30 deficiency reduced the production of endocochlear potential (EP) and the release of ATP, which may have induced hearing loss. Taken together, this study showed that lack of Cx30 can lead to hearing loss with an approximately 30% reduction of Cx26 in the present Cx30 knockout model. Hence, Cx30 may play an important rather than redundant role in hearing development.
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影响因子：
2.8
作者：
KRAUS, HJ;AULBACHKRAUS, K
通讯作者：
AULBACHKRAUS, K
影响因子：
5.3
作者：
Guo L;Cao W;Niu Y;He S;Chai R;Yang J
通讯作者：
Yang J
影响因子：
3.3
作者：
Chen J;Zhao HB
通讯作者：
Zhao HB
DOI：
10.1007/bf00186783
发表时间：
1995-02-01
期刊：
ANATOMY AND EMBRYOLOGY
影响因子：
--
作者：
KIKUCHI, T;KIMURA, RS;ADAMS, JC
通讯作者：
ADAMS, JC
DOI：
10.3390/life10110258
发表时间：
2020-10-28
期刊：
Life (Basel, Switzerland)
影响因子：
--
作者：
Adadey SM;Wonkam-Tingang E;Twumasi Aboagye E;Nayo-Gyan DW;Boatemaa Ansong M;Quaye O;Awandare GA;Wonkam A
通讯作者：
Wonkam A