FUNCTIONAL STUDIES OFNR2E3 IN RETINAL DEVELOPMENT

RD/RD7突变小鼠在一个月大时表现出视网膜退化，在整个视网膜上有白色、均匀分布的斑点，随后在16个月大时出现斑驳的视网膜色素沉着和50%的光感受器细胞退化。RD7小鼠携带光感受器细胞特异性核受体(NR2E3)基因的突变。人类NR2E3基因突变与一种独特的视网膜营养不良-增强型S圆锥综合征(ESCS)有关。大多数遗传性人类视网膜疾病通过凋亡机制减少花叶中的受体数量，从而影响成熟的光感受器的分布。一个常见的发现是，致病的光感受器特异基因会改变这些细胞内的关键结构或功能，从而导致细胞死亡。ESCs的独特之处在于，它表现为一种更多的光感受器亚型，表现为最少的视锥细胞亚型S视锥细胞显著增加；伴有不同程度的视网膜变性。本研究的目的是研究mNR2E3的功能特征，并深入了解参与视网膜正确发育和功能的机制。这一目标将通过以下目的来实现：1.确定NR2E3的时空表达模式；2.识别与NR2E3相互作用的因子；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.