早老素
PSEN1型
转基因小鼠
转基因
表型
淀粉样前体蛋白
神经科学
阿尔茨海默病
生物
背景(考古学)
基因敲除
疾病
人性化鼠标
神经退行性变
基因剔除小鼠
基因
遗传学
医学
病理
体内
古生物学
作者
Naoto Watamura,Kaori Sato,Takaomi C. Saido
标识
DOI:10.1016/j.neuint.2022.105361
摘要
Most mouse models for preclinical research into Alzheimer's disease (AD) rely on the overexpression paradigm, in which familial AD (FAD)-related genes linked to amyloid precursor protein (APP) and presenilin-1 (PSEN1) are overexpressed. Such mice have been used for over two decades as the first-generation transgenic lines for AD, with animals exhibiting AD pathologies along with additional phenotypes, leading to the serious artifacts. To overcome the intrinsic drawbacks of the overexpression paradigm, we previously developed second-generation mouse models that incorporate humanized amyloid β (Aβ) sequences and several FAD-related mutations on the mouse endogenous App gene. Such models show AD pathologies in an age-dependent manner. In addition, our group recently generated additional lines of mice harboring multiple mutations without gene overexpression; these third-generation models exhibit an accelerated AD pathology compared to earlier generations. In this review, we describe the development and future prospects of AD mouse models in terms of their scientific properties and therapeutic perspectives in the context of the preclinical study of AD.
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