MOLECULAR BASIS OF JUVENILE NCL

幼体 NCL 的分子基础

• 批准号: 6096741
• 负责人: TERRY J LERNER
• 金额: $ 1.5万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6096741
• 关键词: adolescence (12-20); child (0-11); chimeric proteins; clinical research; gene expression; gene mutation; human subject; laboratory mouse; neuronal ceroid lipofuscinosis; organelles; protein structure function; proteins

DESCRIPTION: The long-term objective of the work proposed is to understand the molecular basis of neuronal ceroid lipofuscinosis (NCL), the most common neurodegenerative disorder of childhood. NCL refers to a group of inherited disorders characterized by loss of vision, seizures, and progressive mental deterioration. The hallmark of these diseases is the accumulation of autofluorescent lipopigments in storage bodies found in the brain and peripheral tissues. The biochemical basis of NCL remains unknown and there is no treatment effective in delaying or preventing the progression of this fatal disorder. The applicant and her colleagues recently succeeded in isolating the gene for juvenile NCL, CLN3. This gene encodes a protein of as yet unknown function. It is the goal of the application to establish the normal function of this protein. The investigators will study the pattern of expression and cellular localization of CLN3, which may identify specific subcellular organelles or biochemical pathways as important in the pathogenesis of JNCL. They will also identify proteins that interact with CLN3, which may implicate specific protein-protein interactions along these pathways. Finally, they will insertionally inactivate the mouse CLN3 gene, which may reveal clues as to the role of CLN3 in development. These knock-out mice may prove valuable for studying the mechanism of the disease and for evaluating new therapies. The combined results of these studies should provide the basis for formulating hypotheses concerning the normal function of CLN3, and provide a better understanding of the pathogenesis and potential treatment of the disease.

描述：提出的工作的长期目标是了解 最常见的神经性蜡样脂褐素沉积症(NCL)的分子基础 儿童期的神经退行性疾病。NCL指的是一组继承的 以失明、癫痫和进行性精神障碍为特征的疾病 恶化。这些疾病的特点是 在大脑和大脑中发现的储存体中的自体荧光脂素 周围组织。NCL的生化基础仍不清楚，而且 是否没有有效的治疗方法来延缓或阻止这种疾病的进展 致命性紊乱。申请人和她的同事最近成功地 NCL幼虫CLN3基因的分离。该基因编码一种蛋白质 目前尚不清楚其功能。应用程序的目标是建立 这种蛋白质的正常功能。调查人员将研究这种模式 CLN3的表达和细胞定位，这可能识别特定的 亚细胞细胞器或生化途径在 JNCL的发病机制。他们还将识别与之相互作用的蛋白质。 CLN3，这可能涉及沿着这些基因的特定的蛋白质-蛋白质相互作用 小路。最后，他们将插入灭活小鼠CLN3基因， 这可能会揭示CLN3在发育中的作用。这些 基因敲除小鼠可能被证明对研究这种疾病的机制很有价值 以及评估新的治疗方法。这些研究的综合结果 应该为提出关于常态的假设提供基础 CLN3的功能，并为更好地理解其发病机制和 这种疾病的潜在治疗方法。