Cataractogenesis, Connexin Mutants and Genetic Modifier(s)

项目摘要 遗传变异、环境应激因素和衰老可引发晶状体细胞的病理状态 导致不同类型的白内障。以往的研究表明，晶状体的出生后发病和严重程度 核性白内障受连接蛋白46(Cx46)功能缺失的影响，遗传变异包括 小鼠品系C57BL/6J(B6)和129 Svjae(129)之间存在CP49和周轴蛋白(Prx)。这项研究 一项提案将评估关于细胞间缝隙连接如何由Cx46和Prx组成的新假设 介导膜/细胞骨架复合体协同调节晶状体内纤维细胞形态发生 晶状体透明所需的钙平衡。该项目将提供一个全面的机制 了解晶状体纤维的钙离子内流和外流以及互锁结构 由黏附和运输镶嵌系统调节和维持，包括缝隙连接、AQP0、钙 通过Prx等支架蛋白连接到细胞骨架的通道。这项研究项目的完成将 还提供了关于常见小鼠品系(如C57BL/6J)之间的遗传变异的基本知识 给镜头研究界的是129个。

Project Summary Genetic variances, environmental stress factors and aging can initiate pathological conditions in lens cells leading to different types of cataracts. Previous studies show that the postnatal onset and severity of lens nuclear cataracts are impacted by a functional loss of connexin 46 (Cx46) with genetic variances including CP49 and periaxin (Prx) occurred between mouse strains C57BL/6J (B6) and 129 Svjae (129). This research proposal will evaluate novel hypotheses about how intercellular gap junctions consisting of Cx46 and Prx mediated membrane/cytoskeletal complexes coordinately regulate interior lens fiber cell morphogenesis and calcium homeostasis needed for lens transparency. This project will provide a comprehensive mechanistic understanding about how calcium influx and efflux as well as interlocking structures of lens fibers are regulated and maintained by the adhesion and transport mosaic systems including gap junctions, Aqp0, calcium channels linked to cytoskeletons through scaffold proteins such as Prx. Completion of this research project will also provide essential knowledge about genetic variations among common mouse strains such as C57BL/6J and 129 to the lens research community.