APOE-TOMM40人性化小鼠模型:年龄,性别和多T变异对基因表达的影响的表征
William K Gottschalk1, Scott Mahon1, Dellila Hodgson1,2
1Division of Translational Brain Sciences, Department of Neurology, Duke University Medical Center, Durham, NC, USA.
Journal of Alzheimer's disease : JAD
|July 17, 2023
概括
研究人员为APOE-TOMM40基因创建了一个新的人性化小鼠模型,以研究晚发性阿尔茨海默病 (LOAD). 这个模型揭示了TOMM40多T基因型,性别和年龄如何影响各种组织中的基因表达.
科学领域:
- 遗传学 是一个遗传学.
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 人类染色体19的19q13.32区域富含基因,与晚发性阿尔茨海默病 (LOAD) 和其他与年龄相关的疾病有关.
- 了解影响LOAD的遗传和监管因素对于开发有效治疗非常重要.
研究的目的:
- 开发第一个人性化的小鼠模型,包括人类TOMM40和APOE基因,包括所有内基,基因间基因和调节序列.
- 调查TOMM40 '523'多T基因型,性别和年龄对人类APOE和TOMM40基因表达 in vivo的影响.
主要方法:
- 通过使用重组,将鼠标的APOE-TOMM40区域替换为人类的正统模型来生成一个人性化的小鼠模型.
- 人类TOMM40和APOEmRNA表达在小鼠大脑,肝脏和脏组织中的定量通过TaqMan测试.
主要成果:
- 这种人性化的小鼠模型成功地表达了人类的TOMM40和APOE基因.
- 确定了"523"多T基因型,性别和年龄对人类TOMM40和APOEmRNA水平的显著组织特异性和共享调节效应.
- "523"多T基因型在所有研究的器官中都表现出调节作用.
结论:
- 开发的人性化小鼠模型为研究LOAD和相关条件的遗传和调节机制提供了一个有价值的平台.
- 该模型促进了基础研究,转化研究和针对APOE基因组区域的临床前药物发现.
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