MOLECULAR BASIS OF JUVENILE NCL

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， 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。

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.