TRANSGENIC MOUSE MODEL FOR ALZHEIMER'S DISEASE

阿尔茨海默病转基因小鼠模型

• 批准号: 3487936
• 负责人: VEMURI REDDY
• 金额: $ 4.84万
• 依托单位: TSI CORPORATION
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-09-01 至 1991-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3487936
• 关键词: Alzheimer's disease; amyloid proteins; disease /disorder model; embryo /fetus; embryo /fetus preservation; fusion gene; gene expression; genetic manipulation; genetically modified animals; laboratory mouse; model design /development; neoplastic cell culture for noncancer research; neuritic plaques; pheochromocytoma; transfection

TSI proposes to develop a transgenic mouse model for Alzheimer's Disease (AD), a devastating degenerative disorder of the brain that is the leading cause of dementia among the elderly. AD is characterized by cerebrovascular amyloid deposits, endocortical plaques and neurofibrillary tangles. The predominant component of these structures is b-amyloid protein (bAP). This is encoded by part of a larger gene for amyloid precursor protein (APP), which has been cloned, mapped, and partially characterized. Recent data suggest that in AD, BAP is cleaved from APP and deposited in amyloid plaques as a result of abnormal precursor processing (Tanzi et al., 1989). Increasing the APP gene dosage in cultured cells by transfecting the human APP gene induces overproduction of protein determinants including bAP (Marotta et al., 1989). Although increased gene dosage of APP is not found in AD, it may be sufficient for amyloid plaque formation. Therefore, the transfer of human APP into mice may confer an effective increase in gene dosage that predisposes them to amyloid plaques deposits. These mice may be used to study the relationship between APP expression, amyloid processing, and plaque formation. Such mice would be valuable model for exploring both pathophysiology and potential palliative treatments for the human disorder.

TSI建议开发阿尔茨海默病转基因小鼠模型 (AD)，一种毁灭性的大脑退行性疾病，它是 导致老年人痴呆症的原因。广告的特点是 脑血管淀粉样沉积、皮质内斑块和神经原纤维 唐格斯。这些结构的主要成分是b-淀粉样蛋白。 蛋白质(BaP)。这是由一个更大的淀粉样蛋白基因的一部分编码的 前体蛋白(APP)，已被克隆、定位和部分 特色化的。最近的数据表明，在AD中，BAP从APP和 由于前体异常加工而沉积在淀粉样斑块中 (坦桑尼亚等人，1989年)。通过增加APP基因在培养细胞中的剂量 转染人APP基因可诱导蛋白质过量生产 决定因素包括苯并苯(Marotta等人，1989年)。虽然增加了基因 AD患者未发现APP剂量，可能足以治疗淀粉样斑块 队形。因此，将人类APP转移到小鼠体内可能会授予一种 有效增加易患淀粉样斑块的基因剂量 押金。这些小鼠可能被用来研究APP之间的关系 表达、淀粉样蛋白的加工和斑块的形成。这样的老鼠会是 探索病理生理学和潜在的姑息治疗的有价值的模型 人类疾病的治疗方法。