BATTEN DISEASE

这个项目试图定义先天的生化异常 儿童遗传性神经退行性疾病，称为神经元 蜡样脂褐素增多症(NCL，巴顿病)。这是一个延续 目前的工作使用了绵羊模型和比较研究，但有所改变 专注于细胞生物学研究，并扩展合作 芬兰的哈尔蒂亚博士专门研究这种婴儿形态。 这种形式不同于绵羊和晚期婴幼儿和幼年羊。 线粒体三磷酸腺苷合成酶c亚单位的形式和其他 特别是积累起来的。在绵羊身上学到的经验和技能 项目及其对人类形态的延伸将应用于 婴幼儿疾病中储存材料的特征。从… 特定积累物种的性质，一种策略将是 为确定潜在的生化损伤而开发。抗体 将生产用于光和电子的免疫细胞化学研究 微观层面。 绵羊的工作将集中在确定c亚基的具体途径上。 周转，从它的合成，合并到线粒体和通过 它的正常降解。不同形式的c亚基存储NCL反映 影响该途径中不同相关蛋白的突变 而不是单一基因产物的不同突变。比较研究 不同形式的NCL将有助于定义这一途径。这个 方法学将利用新开发的放射性标记大肠杆菌 在细胞培养中表达c亚基(带有前导序列)和 通过对指定的特征进行表征来加强重建研究 亚细胞隔间。针对不同表位的抗体 包括前导序列和成熟亚基c以及 特殊的细胞器将用于免疫细胞化学研究。 对根本缺陷的界定(S)将具有更好的意义 诊断方法，包括产前诊断和杂合子 检测并可能与治疗相关。鉴于……的重要性 ATP合成酶复合体，该项目也将与 了解其装配和拆卸过程。

This project seeks to define the inborn biochemical anomalies in the inherited neuro-degenerative diseases of children known as the neuronal ceroid-lipofuscinoses (NCL, Batten disease). It is a continuation of present work using the ovine model and comparative studies, with a change of focus to cellular biology investigations and extends collaboration with Dr. Haltia of Finland specifically investigating the infantile form. This form is distinct from the ovine and late infantile and juvenile forms and others where subunit c of mitochondrial ATP synthase specifically accumulates. The experience and skills learned in the ovine project and its extension of human forms will be applied to the characterization of the storage material in the infantile disease. From the Nature of specifically accumulated species, a strategy will be developed to determine the underlying biochemical lesion. Antibodies will be produced for immunocytochemical studies at light and electron microscopic levels. The ovine work will focus on defining the specific pathway of subunit c turnover, from its synthesis, incorporation into mitochondria and through its normal degradation. Different forms of subunit c storage NCL reflect mutations affecting different associated proteins in this pathway rather than different mutations of a single gene product. Comparative studies with different forms of NCL will help define this pathway. The methodologies will exploit the newly developed radiolabelled E. coli expressed subunit c (with lead sequences) in cell culture and reconstitution studies augmented by characterization of indicated subcellular compartments. Antibodies against different epitopes including lead sequences and mature subunit c as well as markers for particular organelles will be used in immunocytochemical studies. Definition of the underlying defect(s) would have significance for better methods of diagnosis, including prenatal diagnosis and heterozygote detection and may have relevance to therapy. Given the significance of ATP synthase complex, the project will also have relevance to understanding of its assembly and disassembly.