Trends in Cell Biology ( IF 19.0 ) Pub Date : 2021-08-21 , DOI: 10.1016/j.tcb.2021.07.007 Dale W Laird 1 , Paul D Lampe 2
The 21-member connexin gene family exhibits distinct tissue expression patterns that can cause a diverse array of over 30 inherited connexin-linked diseases ranging from deafness to skin defects and blindness. Intriguingly, germline mutations can cause disease in one tissue while other tissues that abundantly express the mutant connexin remain disease free, highlighting the importance of the cellular context of mutant expression. Modeling connexin pathologies in genetically modified mice and tissue-relevant cells has informed extensively on no less than a dozen gain- and loss-of-function mechanisms that underpin disease. This review focuses on how a deeper molecular understanding of the over 930 mutations in 11 connexin-encoding genes is foundational for creating a framework for therapeutic interventions.
中文翻译:
基于连接蛋白的遗传病的细胞机制
由 21 个成员组成的连接蛋白基因家族表现出不同的组织表达模式,可导致 30 多种遗传性连接蛋白相关疾病,从耳聋到皮肤缺陷和失明。有趣的是,种系突变可在一个组织中引起疾病,而大量表达突变连接蛋白的其他组织则保持无病状态,这突显了突变表达的细胞环境的重要性。对转基因小鼠和组织相关细胞中的连接蛋白病理学进行建模已广泛了解不少于十几种支持疾病的功能获得和丧失机制。本综述侧重于对 11 个连接蛋白编码基因中 930 多个突变的更深入的分子理解如何成为创建治疗干预框架的基础。