| Co-editing PINK1 and DJ-1 Genes Via Adeno-Associated Virus-Delivered CRISPR/Cas9 System in Adult Monkey Brain Elicits Classical Parkinsonian Phenotype |
| Li, H; Wu, SH; Ma, X; Li, X ; Cheng, TL; Chen, ZF; Wu, J; Lv, LB; Li, L; Xu, LQ; Wang, WC; Hu, YZ; Jiang, HS; Yin, Y; Qiu, ZL; Hu, XT
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| 2021
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| 发表期刊 | NEUROSCIENCE BULLETIN
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| ISSN | 1673-7067
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| 卷号 | 37期号:9页码:1271-1288 |
| 摘要 | Whether direct manipulation of Parkinson's disease (PD) risk genes in the adult monkey brain can elicit a Parkinsonian phenotype remains an unsolved issue. Here, we used an adeno-associated virus serotype 9 (AAV9)-delivered CRISPR/Cas9 system to directly co-edit PINK1 and DJ-1 genes in the substantia nigras (SNs) of two monkey groups: an old group and a middle-aged group. After the operation, the old group exhibited all the classic PD symptoms, including bradykinesia, tremor, and postural instability, accompanied by key pathological hallmarks of PD, such as severe nigral dopaminergic neuron loss (>64%) and evident alpha-synuclein pathology in the gene-edited SN. In contrast, the phenotype of their middle-aged counterparts, which also showed clear PD symptoms and pathological hallmarks, were less severe. In addition to the higher final total PD scores and more severe pathological changes, the old group were also more susceptible to gene editing by showing a faster process of PD progression. These results suggested that both genetic and aging factors played important roles in the development of PD in the monkeys. Taken together, this system can effectively develop a large number of genetically-edited PD monkeys in a short time (6-10 months), and thus provides a practical transgenic monkey model for future PD studies. |
| 收录类别 | sci
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| 语种 | 英语
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| 文献类型 | 期刊论文
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| 条目标识符 | http://ir.kiz.ac.cn/handle/152453/13267
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| 专题 | 科研部门_神经系统编码（胡新天）
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推荐引用方式
GB/T 7714 |
Li, H,Wu, SH,Ma, X,et al. Co-editing PINK1 and DJ-1 Genes Via Adeno-Associated Virus-Delivered CRISPR/Cas9 System in Adult Monkey Brain Elicits Classical Parkinsonian Phenotype[J]. NEUROSCIENCE BULLETIN,2021,37(9):1271-1288.
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| APA |
Li, H.,Wu, SH.,Ma, X.,Li, X.,Cheng, TL.,...&Hu, XT.(2021).Co-editing PINK1 and DJ-1 Genes Via Adeno-Associated Virus-Delivered CRISPR/Cas9 System in Adult Monkey Brain Elicits Classical Parkinsonian Phenotype.NEUROSCIENCE BULLETIN,37(9),1271-1288.
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| MLA |
Li, H,et al."Co-editing PINK1 and DJ-1 Genes Via Adeno-Associated Virus-Delivered CRISPR/Cas9 System in Adult Monkey Brain Elicits Classical Parkinsonian Phenotype".NEUROSCIENCE BULLETIN 37.9(2021):1271-1288.
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