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MOLECULAR BASIS OF JUVENILE NCL

幼体 NCL 的分子基础

基本信息

批准号：
6188142
负责人：
Marcy MACDONALD
金额：
$ 28.73万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
1993
资助国家：
美国
起止时间：
1993-08-01 至 2002-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6188142
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

项目摘要

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：拟议工作的长期目标是了解神经元蜡样质脂褐质沉积症（NCL）的分子基础，儿童神经退行性疾病 NCL是指一组遗传性以视力丧失、癫痫发作和进行性精神障碍为特征的疾病恶化这些疾病的标志是在大脑中发现的储存体中的自体荧光脂色素，外周组织 NCL的生化基础仍然未知，并且存在没有有效的治疗方法可以延缓或阻止这种疾病的进展，致命的疾病申请人和她的同事最近成功地分离幼年NCL基因CLN 3。该基因编码一种蛋白质，未知的功能。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 CLN 3的表达和细胞定位，这可能会识别特定的亚细胞器或生物化学途径， JNCL的发病机制。他们还将鉴定出与蛋白质相互作用的 CLN 3，这可能涉及特定的蛋白质-蛋白质相互作用沿着这些途径。最后，他们将插入小鼠CLN 3基因，这可能揭示CLN 3在发育中的作用的线索。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疗法。这些研究的综合结果应该为制定关于正常的假设提供基础 CLN 3的功能，并提供更好的了解发病机制，潜在的治疗疾病。