Motor dysfunction and neurodegeneration in a C9orf72 mouse line expressing poly-PR

doi:10.1038/s41467-019-10956-w

	Motor dysfunction and neurodegeneration in a C9orf72 mouse line expressing poly-PR
	Hao, Zongbing 1,2; Liu, Liu 1,2; Tao, Zhouteng 3; Wang, Rui 1,2; Ren, Haigang 1,2; Sun, Hongyang 1,2; Lin, Zixuan 1,2; Zhang, Zhixiong 1,2; Mu, Chenchen 1,2; Zhou, Jiawei 4
刊名	NATURE COMMUNICATIONS
	2019-07-02
卷号	10 页码:11
ISSN号	2041-1723
DOI	10.1038/s41467-019-10956-w
通讯作者	Wang, Guanghui(wanggh@suda.edu.cn)
英文摘要	A GGGGCC hexanucleotide repeat expansion in intron 1 of chromosome 9 open reading frame 72 (C9ORF72) gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Repeat-associated non-ATG translation of dipeptide repeat proteins (DPRs) contributes to the neuropathological features of c9FTD/ALS. Among the five DPRs, arginine-rich poly-PR are reported to be the most toxic. Here, we generate a transgenic mouse line that expresses poly-PR (GFP-PR28) specifically in neurons. GFP-PR28 homozygous mice show decreased survival time, while the heterozygous mice show motor imbalance, decreased brain weight, loss of Purkinje cells and lower motor neurons, and inflammation in the cerebellum and spinal cord. Transcriptional analysis shows that in the cerebellum, GFP-PR28 heterozygous mice show differential expression of genes related to synaptic transmission. Our findings show that GFP-PR28 transgenic mice partly model neuropathological features of c9FTD/ALS, and show a role for poly-PR in neurodegeneration.
WOS关键词	HEXANUCLEOTIDE REPEAT EXPANSION ; AMYOTROPHIC-LATERAL-SCLEROSIS ; RNA FOCI ; PROTEINS ; TDP-43 ; PATHOLOGY ; TOXICITY ; DEGENERATION ; INFLAMMATION ; INCLUSIONS
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000473425300003
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/289299]
专题	中国科学院上海药物研究所
通讯作者	Wang, Guanghui
作者单位	1.Soochow Univ, Coll Pharmaceut Sci, Jiangsu Key Lab Neuropsychiat Dis, Lab Mol Neuropathol, Suzhou 215123, Jiangsu, Peoples R China 2.Soochow Univ, Coll Pharmaceut Sci, Dept Pharmacol, Suzhou 215123, Jiangsu, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Ctr Drug Safety Evaluat & Res, Shanghai 201203, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Biol Sci, Ctr Excellence Brain Sci, Inst Neurosci,State Key Lab Neurosci, Shanghai 200031, Peoples R China
推荐引用方式 GB/T 7714	Hao, Zongbing,Liu, Liu,Tao, Zhouteng,et al. Motor dysfunction and neurodegeneration in a C9orf72 mouse line expressing poly-PR[J]. NATURE COMMUNICATIONS,2019,10:11.
APA	Hao, Zongbing.,Liu, Liu.,Tao, Zhouteng.,Wang, Rui.,Ren, Haigang.,...&Wang, Guanghui.(2019).Motor dysfunction and neurodegeneration in a C9orf72 mouse line expressing poly-PR.NATURE COMMUNICATIONS,10,11.
MLA	Hao, Zongbing,et al."Motor dysfunction and neurodegeneration in a C9orf72 mouse line expressing poly-PR".NATURE COMMUNICATIONS 10(2019):11.