Institutional Repository of Key Laboratory of Mental Health, CAS
An App knock-in rat model for Alzheimer's disease exhibiting A beta and tau pathologies, neuronal death and cognitive impairments | |
Pang, Keliang1,2,3; Jiang, Richeng4,5; Zhang, Wei6,7; Yang, Zhengyi8; Li, Lin-Lin9,10; Shimozawa, Makoto4; Tambaro, Simone4; Mayer, Johanna4; Zhang, Baogui8; Li, Man6,7; Wang, Jiesi6,7; Liu, Hang1,2,3; Yang, Ailing1; Chen, Xi9,10; Liu, Jiazheng9,10; Winblad, Bengt4,11; Han, Hua9,10; Jiang, Tianzi8; Wang, Weiwen6,7; Nilsson, Per4; Guo, Wei1,2,3; Lu, Bai1,2,3 | |
第一作者 | Keliang Pang |
通讯作者邮箱 | wguo@tsinghua.edu.cn (guo, wei) ; bai_lu@tsinghua.edu.cn (lu, bai) |
心理所单位排序 | 6 |
摘要 | A major obstacle in Alzheimer's disease (AD) research is the lack of predictive and translatable animal models that reflect disease progression and drug efficacy. Transgenic mice overexpressing amyloid precursor protein (App) gene manifest non-physiological and ectopic expression of APP and its fragments in the brain, which is not observed in AD patients. The App knock-in mice circumvented some of these problems, but they do not exhibit tau pathology and neuronal death. We have generated a rat model, with three familiar App mutations and humanized A beta sequence knocked into the rat App gene. Without altering the levels of full-length APP and other APP fragments, this model exhibits pathologies and disease progression resembling those in human patients: deposit of A beta plaques in relevant brain regions, microglia activation and gliosis, progressive synaptic degeneration and AD-relevant cognitive deficits. Interestingly, we have observed tau pathology, neuronal apoptosis and necroptosis and brain atrophy, phenotypes rarely seen in other APP models. This App knock-in rat model may serve as a useful tool for AD research, identifying new drug targets and biomarkers, and testing therapeutics. |
2021-11-17 | |
DOI | 10.1038/s41422-021-00582-x |
发表期刊 | CELL RESEARCH |
ISSN | 1001-0602 |
页码 | 19 |
期刊论文类型 | 综述 |
收录类别 | SCI ; CSCD |
资助项目 | National Key Research and Development Program of China[2017YFE0126500] ; National Natural Science Foundation of China[81861138013] ; National Natural Science Foundation of China[81501105] ; National Natural Science Foundation of China[31730034] ; Beijing Advanced Innovation Center for Human Brain Protection, Shenzhen Science Technology and Innovation Commission[JCYJ20170411152419928] ; Beijing Advanced Innovation Center for Human Brain Protection, Shenzhen Science Technology and Innovation Commission[JCYJ20180508152240368] ; Beijing Municipal Science & Technology Commission[Z151100003915118] ; Strategic Priority Research Program of Chinese Academy of Science[XDB32030200] ; Hallstens forskningsstiftelse ; Swedish Research Council ; Swedish Brain foundation ; Swedish Alzheimer foundation ; Margaretha af Ugglas Foundation ; China Scholarship Council ; H2020-MSCA-ITN-2019[860035] |
出版者 | SPRINGERNATURE |
WOS关键词 | AMYLOID-PRECURSOR-PROTEIN ; TRANSGENIC MICE ; MOUSE MODELS ; SEX ; ISOFORMS ; MUTATION ; MEMORY ; AGE ; NEURODEGENERATION ; NEUROPATHOLOGY |
WOS研究方向 | Cell Biology |
WOS类目 | Cell Biology |
WOS记录号 | WOS:000719692600001 |
WOS分区 | Q1 |
资助机构 | National Key Research and Development Program of China ; National Natural Science Foundation of China ; Beijing Advanced Innovation Center for Human Brain Protection, Shenzhen Science Technology and Innovation Commission ; Beijing Municipal Science & Technology Commission ; Strategic Priority Research Program of Chinese Academy of Science ; Hallstens forskningsstiftelse ; Swedish Research Council ; Swedish Brain foundation ; Swedish Alzheimer foundation ; Margaretha af Ugglas Foundation ; China Scholarship Council ; H2020-MSCA-ITN-2019 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://ir.psych.ac.cn/handle/311026/41213 |
专题 | 中国科学院心理健康重点实验室 |
通讯作者 | Guo, Wei; Lu, Bai |
作者单位 | 1.Tsinghua Univ, Tsinghua Univ Peking Univ Joint Ctr Life Sci, Sch Pharmaceut Sci, IDG McGovern Inst Brain Res, Beijing, Peoples R China 2.Res Inst Tsinghua Univ Shenzhen, R&D Ctr Diag & Treatment Major Brain Dis, Shenzhen, Guangdong, Peoples R China 3.Capital Med Univ, Adv Innovat Ctr Human Brain Protect, Beijing Tiantan Hosp, Beijing, Peoples R China 4.Karolinska Inst, Ctr Alzheimer Res, Div Neurogeriatr, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden 5.First Hosp Jilin Univ, Dept Otorhinolaryngol Head & Neck Surg, Changchun, Peoples R China 6.Chinese Acad Sci, Inst Psychol, CAS Key Lab Mental Hlth, Beijing, Peoples R China 7.Univ Chinese Acad Sci, Dept Psychol, Beijing, Peoples R China 8.Chinese Acad Sci, Brainnetome Ctr, Inst Automat, Beijing, Peoples R China 9.Univ CAS, Sch Future Technol, Res Ctr Brain Inspired Intelligence, Inst Automat,Natl Lab Pattern Recognit, Shanghai, Peoples R China 10.Chinese Acad Sci, CAS Ctr Excellence Brain Sci & Intelligence Techn, Shanghai, Peoples R China 11.Karolinska Univ Hosp, Theme Aging, Huddinge, Sweden |
推荐引用方式 GB/T 7714 | Pang, Keliang,Jiang, Richeng,Zhang, Wei,et al. An App knock-in rat model for Alzheimer's disease exhibiting A beta and tau pathologies, neuronal death and cognitive impairments[J]. CELL RESEARCH,2021:19. |
APA | Pang, Keliang.,Jiang, Richeng.,Zhang, Wei.,Yang, Zhengyi.,Li, Lin-Lin.,...&Lu, Bai.(2021).An App knock-in rat model for Alzheimer's disease exhibiting A beta and tau pathologies, neuronal death and cognitive impairments.CELL RESEARCH,19. |
MLA | Pang, Keliang,et al."An App knock-in rat model for Alzheimer's disease exhibiting A beta and tau pathologies, neuronal death and cognitive impairments".CELL RESEARCH (2021):19. |
条目包含的文件 | ||||||
文件名称/大小 | 文献类型 | 版本类型 | 开放类型 | 使用许可 | ||
An App knock-in rat (9645KB) | 期刊论文 | 出版稿 | 限制开放 | CC BY-NC-SA | 请求全文 |
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