Testing compounds for effects on synaptophysin in transgenic mice expressing an Alzheimer's disease FAD DNA sequence
    12.
    发明授权
    Testing compounds for effects on synaptophysin in transgenic mice expressing an Alzheimer's disease FAD DNA sequence 有权
    测试化合物对表达阿尔茨海默病FAD DNA序列的转基因小鼠中突触素的影响

    公开(公告)号:US07186881B2

    公开(公告)日:2007-03-06

    申请号:US10746473

    申请日:2003-12-23

    摘要: The construction of transgenic animal models of human Alzheimer's disease, and methods of using the models to screen potential Alzhe## disease therapeutics, are described. The models are characterized by pathologies similar to pathologies observed in Alzheimer's disease, based on expression of all three forms of the β-amyloid precursor protein (APP), APP695, APP751, and APP770, as well as various point mutations based on naturally occurring mutations, such as the London and Indiana familial Alzheimer's disease (FAD) mutations at amino acid 717, predicted mutations in the APP gene, and truncated forms of APP that contain the Aβ region. Animal cells can be isolated from the transgenic animals or prepared using the same constructs with standard techniques such as lipofection or electroporation. The transgenic animals, or animal cells, are used to screen for compounds altering the pathological course of Alzheimer's disease as measured by their effect on the amount of APP, β-amyloid peptide, and numerous other Alzheimer's disease markers in the animals, the neuropathology of the animals, as well as by behavioral alterations in the animals.

    摘要翻译: 描述了人类阿尔茨海默氏病的转基因动物模型的构建,以及使用该模型筛选潜在的阿尔茨海默病治疗剂的方法。 基于所有三种形式的β-淀粉样蛋白前体蛋白(APP),APP695,APP751和APP770的表达以及基于天然存在的突变的各种点突变,模型的特征在于类似于在阿尔茨海默病中观察到的病理学的病理学 ,例如氨基酸717处的伦敦和印第安纳家族性阿尔茨海默病(FAD)突变,APP基因中预测的突变和含有Abeta区的APP的截短形式。 可以从转基因动物中分离动物细胞,或者使用具有标准技术如脂质转染或电穿孔的相同构建体来制备动物细胞。 转基因动物或动物细胞用于筛选改变阿尔茨海默氏病病理过程的化合物,如通过其对动物中APP,β-淀粉样蛋白肽和许多其他阿尔茨海默氏病标志物的量的影响所测量的,神经病理学 动物,以及动物的行为改变。