Cataractogenesis, Connexin Mutants & Genetic Modifier(s)

描述（由申请人提供）： 哺乳动物的透镜在其传输和聚焦光到 视网膜是：1.）一种精细调节的蜂窝间通信网络， 在代谢和电的恒定循环电流下， 透镜单元的耦合，以及2.）精确组织的细胞和分子 建筑，以防止光散射。 分子遗传学研究证实了连接蛋白基因的重要作用 在人类和小鼠的白内障形成中的作用。然而，无论是分子 不同连接蛋白基因间的相互作用和调控机制 在透镜中，也不是白内障发生的分子基础， 这些连接蛋白基因突变体，是众所周知的。此外，它完全是 不知道其他遗传成分如何表现出可变表达， 人类和小鼠中与连接蛋白突变体相关的白内障。 基于文献和我们对自然、自发 连接蛋白突变小鼠与其基因敲除小鼠相比， 假设某些连接蛋白突变体改变了差距的性质 它们形成的连接通道，随后改变了 这一基本的、低阻力的细胞-细胞通路允许细胞通过， 小分子直接扩散在附着的透镜细胞的胞质溶胶之间。 其次，我们假设间隙连接也被用作细胞的一种功能。 质膜中必要的粘附结构成分， 透镜细胞表面结构。 本研究旨在研究细胞间相互作用的机制， 通信和透镜细胞表面结构，这两者都与 连接蛋白基因、其它相关透镜基因和/或其它与晶状体相关的基因的功能 遗传因素（S）。

DESCRIPTION (provided by applicant): Two unique and important features of the mammalian lens in its function of transmitting and focusing light onto the retina are: 1.) a finely regulated cell-cell communication network associated with the standing circulation current for both the metabolic and electrical coupling of lens cells, and 2.) precisely organized cellular and molecular architectures to prevent the light from scattering. Molecular genetic studies have verified the essential role(s) of connexin genes in cataractogenesis in humans and in mice. However, neither the molecular mechanisms for the interaction and regulation between different connexin genes in the lens, nor the molecular basis for the cataractogenesis that is linked to these connexin gene mutants, is well understood. It is, moreover, completely unknown how other genetic components manifest the variable expression of cataracts associated with connexin mutants in humans and in mice. Based on the literature and on our preliminary studies of natural, spontaneous connexin mutant mice in comparison with their gene knockout mice, we hypothesize that some of the connexin mutants change the properties of the gap junction channels which they formed, subsequently altering the permeation of this essential, low-resistance cell-cell pathway that allows for the passage of small molecules directly diffused between the cytosols of attached lens cells. Secondly, we hypothesize that gap junctions are also utilized as one of the necessary adhesive structural components in the plasma membrane for maintaining lens cell surface architecture. The proposed work is designed to study the mechanisms for cell-cell communication and lens cell surface architecture, both of which are related to the function of the connexin genes, other related lens genes, and/or other genetic factor(s).