FUNCTIONAL STUDIES OF MOUSE NR2E3 IN RETINAL DEVELOPMENT

rd/rd 7突变小鼠显示视网膜变性，在1月龄时在其整个视网膜上具有白色均匀间隔的斑点，随后在16月龄时发展成斑驳的视网膜色素沉着和50%的感光细胞变性。rd 7小鼠携带感光细胞特异性核受体（NR 2 E3）基因突变。人NR 2 E3基因突变与一种独特的视网膜营养不良，S锥增强综合征（ESCS）有关。大多数遗传性人类视网膜疾病通过细胞凋亡机制减少嵌合体中受体的数量来影响成熟感光细胞的分布。一个常见的发现是，致病的感光细胞特异性基因改变了这些细胞内的关键结构或功能，导致细胞死亡。ESCS的独特之处在于它表现为更大数量的光感受器亚型，显示出最少的锥亚型S-锥的主要增加;具有不同程度的视网膜变性。本研究的目的是功能性表征mNR 2 E3，并深入了解参与视网膜正确发育和功能的机制。这一目标将通过研究以下目标来实现：1.确定NR 2 E3的时间和空间表达模式，2.鉴定与NR 2 E3相互作用的因子，和3.识别下游效应基因。

The rd/rd7 mutant mice display retinal degeneration and have white, evenly spaced spots over their entire retina at one month of age and subsequently develop mottled retinal pigmentation and a 50% photoreceptor cell degeneration by 16 months of age. The rd7 mouse carries a mutation in the photoreceptor cell-specific nuclear receptor (NR2E3) gene. Mutations in the human NR2E3 gene are associated with a unique retinal dystrophy, Enhanced S Cone syndrome (ESCS). Most inherited human retinal diseases affect mature photoreceptor distribution by reducing the numbers of receptors in the mosaic through apoptotic mechanisms. A common finding is that disease-causing photoreceptor- specific genes alter key structures or functions within these cells that lead to cell death. ESCS is unique in that it manifests as greater numbers of a subtype of photoreceptors, showing a major increase in the least populous cone subtype, the S-cones; with varying degrees of retinal degeneration. The goal of this study is to functional characterize mNR2E3 and gain insight into mechanisms involved in the correct development and function of the retina. This goal will be accomplished by investigating the following aims: 1. determining the temporal and spatial expression pattern of NR2E3, 2. identifying factors that interact with NR2E3, and 3. identifying downstream effector genes.