TRANSGENIC MOUSE MODELS OF HUMAN METABOLIC DISEASES

人类代谢疾病的转基因小鼠模型

• 批准号: 3426089
• 负责人: HENRY J. BAKER
• 金额: $ 2.91万
• 依托单位: WAKE FOREST UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-01 至 1988-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3426089
• 关键词: Tay Sachs disease; beta glucuronidase; complementary DNA; disease /disorder model; gene expression; gene mutation; genetic manipulation; inborn metabolism disorder; model design /development; molecular cloning

Animal models are needed desperately if significant progress is to be made in understanding pathophysiological mechanisms, molecular genetics and therapy of human metabolic diseases. Recent developments in molecular genetics provide the opportunity to create specific analogs of human metabolic diseases in laboratory rodents. Using technology for introduction, stable integration and expression of DNA mediated anti-sense RNA, we propose to demonstrate inhibition of lysosomal Beta-glucuronidase in transgenic mice with expression of lysosomal storage disease resembling mucopolysaccharidosis VII. Successful demonstration of the feasibility of this approach will lead to development of transgenic mouse models of other metabolic diseases for which mutant genes have been cloned and characterized, such as Gm2 gangliosidosis (Tay Sachs disease). This innovative new approach could dramatically advance research on human matabolic diseases by providing critically needed models to define disease mechanisms and develop treatment modalities.

如果要取得重大进展， 在理解病理生理机制方面， 分子遗传学和人类代谢疾病的治疗。 分子遗传学的最新发展提供了 创造人类代谢的特定类似物的机会 实验室啮齿动物的疾病。 将技术用于 DNA介导的导入、稳定整合和表达 反义RNA，我们建议证明抑制 溶酶体β-葡萄糖醛酸酶在转基因小鼠中的表达 类似粘多糖沉积症的溶酶体贮积病 七. 成功论证了这一可行性 这种方法将导致转基因小鼠模型的发展， 其他代谢性疾病，突变基因已被 克隆和表征，如Gm 2神经节苷脂沉积症（Tay Sachs 疾病）。 这种创新的新方法可以大大 人类代谢疾病的研究进展， 急需的模型来定义疾病机制， 制定治疗模式。