FUNCTIONAL CHARACTERIZATION OF NR2E3 IN DEVELOPING AND ADULT PHOTORECEPTOR CELLS

NR2E3 在发育中和成年感光细胞中的功能特征

• 批准号: 8168359
• 负责人: Neena B Haider
• 金额: $ 5.84万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168359
• 关键词: Accounting; Adult; Affect; Biological; Blindness; Clinical; Computer Retrieval of Information on Scientific Projects Database; Defect; Development; Disease; Funding; Generations; Goals; Grant; Institution; Life; Maintenance; Modeling; Mus; Mutation; Nuclear Receptor Gene; Patients; Phenotype; Photoreceptors; Reporting; Research; Research Personnel; Resources; Retina; Retinal; Retinal Cone; Retinal Degeneration; Retinitis Pigmentosa; Role; Source; Syndrome; United States National Institutes of Health; Vision; Visual impairment; emerging adult; improved; mouse model; novel; treatment strategy

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our long-term goal is to understand the biological mechanisms of photoreceptor generation and maintenance, which will enable us to identify novel targets that may be amenable for improved treatment strategies. Our studies have focused on uncovering the transcriptional networks that are directed by the nuclear receptor gene Nr2e3 to modulate photoreceptor development and function. While many past studies have focused on the role of Nr2e3 in the developing retina, its high expression in the adult retina suggests an important function for Nr2e3 in mature photoreceptor cells as well. Furthermore, recent clinical reports have demonstrated that mutations in Nr2e3 not only account for the retinal degeneration observed in patients with enhanced S-cone syndrome (ESCS), but also account for 1-2% of autosomal dominant retinitis pigmentosa, a disease that typically leads to severe visual impairment in early adulthood progressing to severely limited vision or blindness by the fourth or fifth decade of life. We hypothesize that while the rd7 mouse serves as a good model for the excess blue cone cells contributing to the ESCS phenotype, the Nr2e3-Crerho mouse generated for this current study may provide a better model to recapitulate Nr2e3-associated retinitis pigmentosa and retinal degeneration due to loss of Nr2e3 function in the mature retina. With this new mouse model, we are able to study the defects associated with loss Nr2e3 in adult photoreceptor cells without affecting retinal development. We have thus revised this application to focus on the role of Nr2e3 in the mature retina and determine the extent to which loss of Nr2e3 in the mature retina contributes to the rd7 phenotype.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 我们的长期目标是了解光感受器产生和维护的生物学机制，这将使我们能够确定可能适合改善治疗策略的新颖目标。我们的研究集中在揭示由核受体基因NR2E3指导的转录网络调节感光体的发育和功能。尽管过去的许多研究都集中在NR2E3在发展中的视网膜中的作用，但其在成年视网膜中的高表达也表明NR2E3在成熟的光感受器细胞中也具有重要功能。此外，最近的临床报道表明，NR2E3中的突变不仅解释了S-Cone综合征增强（ESC）患者中观察到的视网膜变性，而且还占色素性视网膜炎的1-2％，这种疾病通常会导致早期的现象受到严重限制或盲目的视觉性或盲目的识别。我们假设，尽管RD7小鼠是导致ESC表型的多余蓝色锥细胞的良好模型，但本研究产生的NR2E3-Crerho小鼠可能会​​为NR2E3相关的视网膜炎Pocmentosa和Retinal Deminal deminal nr2e Retnar nr2e Retina nr2e Retina nr2e Retina nr2e nr2e retimina而产生的NR2E3相关性视网膜炎Pocmentosa和Retinal Isalitial deminal deminal。使用这种新的小鼠模型，我们能够研究成年感光细胞中与损失NR2E3相关的缺陷，而不会影响视网膜发育。因此，我们已经修改了此应用，以关注NR2E3在成熟视网膜中的作用，并确定成熟视网膜中NR2E3的损失对RD7表型的损失。