5XFAD转基因小鼠在阿尔茨海默病研究中的应用进展
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山东中医药大学

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国家自然科学基金项目(82205078);山东省自然科学基金项目(ZR2021QH157); 山东省中医药科技项目(2021Q079);山东中医药大学大学生研究训练计划项目(S202210441014,S202310441012,S202310441013)


Advances in the application of 5XFAD transgenic mice in Alzheimer's disease research
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Shandong University of Traditional Chinese Medicine

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Funded by National Natural Science Foundation of China(82205078); Funded by Natural Science Foundation of Shandong Province(ZR2021QH157); Funded by Shandong Province Traditional Chinese Medicine Technology Project(2021Q079);Funded by Innovation and Entrepreneurship training program for college students in Shan Dong University of traditional Chinese Medicine(S202210441014,S202310441012,S202310441013)

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    摘要:

    5×FAD小鼠(Transgenic mice with five familial Alzheimer’s disease)是携带5个家族性基因突变的APP/PS1转基因小鼠,其中与β-淀粉样蛋白前体(amyloid precursor protein,APP)相关的突变为K670N/M671L(Swedish)、1716V(Florida)和V7171(London),与早老素-1(presenilin 1,PS1)相关的突变为MI46L和L286。5×FAD小鼠在1.5月龄时脑内已有大量的β-淀粉样蛋白(β-amyloid,Aβ),2月龄时开始出现神经炎性斑(neuritic plaque,NP)。5×FAD小鼠的病理表型包括淀粉样斑块聚集、神经元丢失、神经胶质细胞增生和记忆功能障碍等。5×FAD小鼠的生物学特性可能涉及脑内Aβ斑块的形成变化、Tau蛋白过度磷酸化、突触功能障碍、神经炎症反应、线粒体功能障碍、血脑屏障损伤、神经元损伤、内质网应激和眼部病变等。作为阿尔茨海默病的经典动物模型,5×FAD转基因小鼠在早期即可模拟AD患者晚期的神经病理过程及行为学表现,被广泛应用于AD发病机制研究和AD新药开发。本文对5×FAD转基因小鼠模型的模型构建、生物学背景、生物学特性及AD防治药物的研发应用进行总结和评述,以期为5×FAD转基因小鼠在AD研究中的应用提供参考与借鉴作用。

    Abstract:

    5×FAD mice (Transgenic mice with five familial Alzheimer's disease) are APP/PS1 transgenic mice carrying five familial gene mutations. With beta-amyloid precursor protein (amyloid precursor protein, APP) related to the mutation of K670N/M671L (Swedish), 1716 v (Florida) and V7171 (London), and the old element - 1 (early presenilin 1, PS1) were MI46L and L286. 5×FAD mice had A large amount of β-amyloid (Aβ) in the brain at 1.5 months of age, and neuritic plaques (NP) began to appear at 2 months of age. The pathological phenotypes of 5×FAD mice included amyloid plaque aggregation, neuronal loss, gliosis, and memory dysfunction.The biological characteristics of 5×FAD mice may involve changes in the formation of brain Aβ plaques, hyperphosphorylation of Tau protein, synaptic dysfunction, neuroinflammatory response, mitochondrial dysfunction, blood-brain barrier injury, neuronal injury, endoplasmic reticulum stress and eye lesions. As a classic animal model of Alzheimer's disease, 5×FAD transgenic mice can simulate the neuropathological process and behavioral manifestations of AD patients in the late stage, and are widely used in the pathogenesis of AD and the development of new drugs for AD. In this paper, the model construction, biological background, biological characteristics of 5×FAD transgenic mice and the development and application of AD prevention and treatment drugs were summarized and reviewed, in order to provide reference for the application of 5×FAD transgenic mice in AD research.

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  • 收稿日期:2023-03-09
  • 最后修改日期:2023-11-15
  • 录用日期:2023-11-16
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