Diverse deafness mechanisms of connexin mutations revealed by studies using in vitro approaches and mouse models.
Diverse deafness mechanisms of connexin mutations revealed by studies using in vitro approaches and mouse models.
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DOI：
10.1016/j.brainres.2009.02.008
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发表时间：
2009-06-24
期刊：
影响因子：
2.9
通讯作者：
Lin X
中科院分区：
文献类型：
--
作者：
Hoang Dinh E;Ahmad S;Chang Q;Tang W;Stong B;Lin X
连接蛋白（Cxs）突变是间隙连接（GJ）细胞间通道的组成蛋白亚基，是最常见的人类遗传缺陷之一，可导致严重的语前非综合征性听力障碍。许多Cxs亚型（如Cxs 26、29、30、31、43）和泛联蛋白（Panxs）在耳蜗中表达，在那里它们有助于形成基于gj的细胞间通信网络。Cx26和Cx30是主要的耳蜗Cxs，它们在大多数GJ斑块中共同聚集形成混合型GJ。特异性Cx亚型的细胞定位为了解耳蜗GJs和半通道的分子结构提供了基础。关于各种共同组装的Cx伙伴之间相互作用的信息对于理解各种类型的基因突变的功能后果至关重要。在细胞系中重组GJs的体外研究已经产生了令人惊讶的由各种Cx突变引起的功能障碍的异质机制。多系cx突变小鼠模型的可用性为耳聋小鼠耳蜗的发病过程提供了一些见解。本文总结了耳蜗GJs的结构和功能方面的最新进展，并对体外研究和小鼠模型中关于Cx突变导致耳蜗细胞死亡和听力损失的机制的最新发现进行了综述。
Mutations in connexins (Cxs), the constitutive protein subunits of gap junction (GJ) intercellular channels, are one of the most common human genetic defects that cause severe prelingual non-syndromic hearing impairments. Many subtypes of Cxs (e.g., Cxs 26, 29, 30, 31, 43) and pannexins (Panxs) are expressed in the cochlea where they contribute to the formation of a GJ-based intercellular communication network. Cx26 and Cx30 are the predominant cochlear Cxs and they co-assemble in most GJ plaques to form hybrid GJs. The cellular localization of specific Cx subtypes provides a basis for understanding the molecular structure of GJs and hemichannels in the cochlea. Information about the interactions among the various co-assembled Cx partners is critical to appreciate the functional consequences of various types of genetic mutations. In vitro studies of reconstituted GJs in cell lines have yielded surprisingly heterogeneous mechanisms of dysfunction caused by various Cx mutations. Availability of multiple lines of Cx-mutant mouse models has provided some insight into the pathogenesis processes in the cochlea of deaf mice. Here we summarize recent advances in understanding the structure and function of cochlear GJs and give a critical review of current findings obtained from both in vitro studies and mouse models on the mechanisms of Cx mutations that lead to cell death in the cochlea and hearing loss.
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影响因子：
3.5
作者：
Bicego, Massimiliano;Beltramello, Martina;Mammano, Fabio
通讯作者：
Mammano, Fabio
DOI：
10.1073/pnas.2233464100
发表时间：
2003-11-11
影响因子：
11.1
作者：
Bruzzone, R;Hormuzdi, SG;Monyer, H
通讯作者：
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影响因子：
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作者：
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通讯作者：
White, TW
影响因子：
3.7
作者：
Batissoco, Ana Carla;Abreu-Silva, Ronaldo Serafim;Mingroni-Netto, Regina Celia
通讯作者：
Mingroni-Netto, Regina Celia
DOI：
10.1016/s0006-291x(02)02517-2
发表时间：
2002-11-15
影响因子：
3.1
作者：
Common, JEA;Becker, D;Kelsell, DP
通讯作者：
Kelsell, DP