METABOLIC BASIS OF CEREBRAL DEGENERATION

脑退化的代谢基础

• 批准号: 3393794
• 负责人: JOHN S O'BRIEN
• 金额: $ 20.07万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-09-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3393794
• 关键词: animal tissue; beta galactosidase; cerebral degeneration; enzyme activity; enzyme structure; gangliosidosis GM1; gene expression; gene mutation; gene therapy; genetic mapping; human tissue; molecular cloning; molecular pathology; mucopolysaccharidosis type IV; nucleic acid sequence; tissue /cell culture; transfection

We plan to define the mutations in human GM1 gangliosidosis, especially patients with the adult form and Morquio Type B. We will pinpoint the mutation in canine GM1 gangliosidosis (Portuguese water dogs) after completing the characterization of the normal canine acid beta-galacto- sidase cDNA. We will express canine and human acid beta-galactosidase cDNA's in several vector systems as a prelude to gene therapy. We plan to assess whether vector-transgene deliver to mutant cells can express sufficient enzyme to achieve metabolic correction and to quantify the amount of enzyme per unit time necessary to achieve this result.

我们计划确定人类GM1神经节苷脂增多症的突变，特别是 患有成人型和B型Morquio的患者。我们将确定 犬神经节苷脂沉积症(葡萄牙水犬)的突变 完成了正常犬酸β-半乳糖的表征- Sidease基因。我们将表达犬类和人类酸性β-半乳糖苷酶 作为基因治疗的前奏，cDNAs存在于几个载体系统中。我们计划 评估载体转基因传递给突变细胞是否可以表达 足够的酶来实现新陈代谢校正和量化 达到这一结果所需的每单位时间所需的酶的量。