Genetic Modifier of the Retinoschisis Gene

但前提是。 我们的研究主要集中在了解人类致病的分子机制 与突触功能和结构缺陷相关的视网膜疾病。X连锁视网膜劈裂 (XLRS)是一种常见的遗传性黄斑变性疾病，由RS1基因突变引起 吉恩。在人类中，受影响的个体在生命的早期阶段表现出严重的中央视力丧失。 视网膜内层分裂，视网膜电波b波消失 (ERG)。B波的丢失表明突触相互作用的功能异常。虽然 RS1功能被预测与细胞黏附有关，这是支持RS1功能的分子途径 疾病和RS1的正常功能在很大程度上是未知的。我们最近发现了一种新的等位基因 由ENU突变产生的44TNJ小鼠中RS1小鼠同源基因Rs1h的突变。 突触异常以及严重的细胞粘连和视网膜板层结构缺陷 已经观察到了突变小鼠。在定位克隆的过程中，我们还发现了一个 改变裂隙表型和板层结构异常的主要修饰基因座。这个 这个项目的目标是了解RS1基因发挥作用的分子途径。 使用小鼠分子遗传学方法。我们的假设是RS1H维持功能 以及视网膜各层的结构完整性，包括突触功能，通过其在细胞中的作用 粘附性，这是由遗传和身体相互作用的因素调节的。在这项提案中，我们的 主要的焦点是鉴定和鉴定Rs1h1(Mori)基因的修饰因子。在目标1中，我们将 进行定位克隆以鉴定Mori基因。在目标2中，我们将测试 RS1H和候选的RS1H结合蛋白。进一步，我们将测试修改器的效果 Rs1Hand是一个候选的RS1H结合分子，由Rs1突变引起表型基因。 ‘

PROVIDED. Our studies are specifically focused on understanding the molecular mechanisms causing human retinal diseases associated with synaptic functional and structural defects. X-linked retinoschisis (XLRS) is a common inherited macular degenerative disease caused by mutations in the RS1 gene. In humans, affected individuals show a significant loss in central vision at early stages of life with a splitting of the inner layers of the retina, and a loss in the b-wave of the electroretinogram (ERG). Loss of the b-wave indicates functional abnormalities in the synaptic interactions. Although RS1 function is predicted to be associated with cell adhesion, molecular pathways underlying the disease and the normal function of RS1 are largely unknown. We recently identified a new allele of the mutation in the RS1 mouse ortholog, Rs1h,in 44TNJ mice created by ENU mutagenesis. Synaptic abnormalities as well as severe cell adhesion and retinal laminar structure defects in mutant mice have been observed. In the course of positional cloning, we also identified a single major modifier locus that changes the schisis phenotype and laminar structure abnormality. The goal of this project is to understand the molecular pathway through which the RS1 gene functions using mouse molecular genetic approaches. Our hypothesis is that RS1H maintains the functional and structural integrity of the retinal layers, including the synaptic function, through its role in cell adhesion, which is regulated by genetically and physically interacting factors. In this proposal, our main focus is to identify and characterize the modifier of the Rs1h1 (Mori) gene. In Aim 1,we will conduct positional cloning to identify the Mori gene. In Aim 2, we will test interaction between RS1H and candidates for RS1H binding proteins. Further, we will test the effect of the modifier gene on phenotypes caused by a mutation in Rs1hand a candidate RS1H binding molecule. '