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Biological implications and limitations of a cynomolgus monkey with naturally occurring Parkinson’s disease

Hao Li Yong-Gang Yao Xin-Tian Hu

Hao Li, Yong-Gang Yao, Xin-Tian Hu. Biological implications and limitations of a cynomolgus monkey with naturally occurring Parkinson’s disease. Zoological Research, 2021, 42(2): 138-140. doi: 10.24272/j.issn.2095-8137.2021.004
Citation: Hao Li, Yong-Gang Yao, Xin-Tian Hu. Biological implications and limitations of a cynomolgus monkey with naturally occurring Parkinson’s disease. Zoological Research, 2021, 42(2): 138-140. doi: 10.24272/j.issn.2095-8137.2021.004

一例自发罹患帕金森病的食蟹猴:生物学意义与研究方向

doi: 10.24272/j.issn.2095-8137.2021.004

Biological implications and limitations of a cynomolgus monkey with naturally occurring Parkinson’s disease

Funds: This work was supported by the Key-Area Research and Development Program of Guangdong Province (2019B030335001), National Key R&D Program of China (2018YFA0801403), and Strategic Priority Research Program of the Chinese Academy of Sciences (XDB32060200 and XDB32020200)
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  • 摘要: 我们发现了首例自发罹患帕金森病的食蟹猴(Li et al, 2020),其临床运动症状典型,包括运动迟缓、姿势异常与静止性震颤等;经典药物治疗的结果类似帕金森病患者的临床表现;组织病理学研究表明中脑黑质多巴胺能神经元的大量丢失(~70%),伴随胞内磷酸化alpha-synuclein的聚集(经典的路易小体早期病理),以及黑质出现路易突起与胶质细胞的增生和激活。基于此,该例自发罹患帕金森病的食蟹猴是非常经典的帕金森病案例,几乎具备帕金森病患者所有的核心表型。遗传分析显示此猴的LRRK2与ATP13A2基因出现了罕见的错义突变。该研究表明帕金森病的发生机制在人类出现以前就产生了,它不是一个人类特有的疾病。因此,利用猴子作为生物医学模型来研究帕金森病是非常可靠的。此猴发病可能与LRRK2突变相关,确切的发病机制需进一步实验证明。综上所述,帕金森病不是人类专属的疾病,利用猴子建立帕金森病模型具有坚实的生物学基础,而LRRK2可作为一个潜在的靶标用来建立转基因帕金森病猴模型。
  • Figure  1.  Spontaneous PD monkey displayed typical Parkinsonian symptoms and pathological hallmarks

    Potential pathogenetic mechanisms are illustrated.

  • [1] Buffalo EA, Movshon JA, Wurtz RH. 2019. From basic brain research to treating human brain disorders. Proceedings of the National Academy of Sciences of the United States of America, 116(52): 26167−26172. doi: 10.1073/pnas.1919895116
    [2] Chen YC, Yu JH, Niu YY, Qin DD, Liu HL, Li G, et al. 2017. Modeling rett syndrome using TALEN-Edited MECP2 mutant cynomolgus monkeys. Cell, 169(5): 945−955.e10. doi: 10.1016/j.cell.2017.04.035
    [3] Fan Y, Howden AJM, Sarhan AR, Lis P, Ito G, Martinez TN, et al. 2018. Interrogating Parkinson's disease LRRK2 kinase pathway activity by assessing Rab10 phosphorylation in human neutrophils. Biochemistry Journal, 475(1): 23−44. doi: 10.1042/BCJ20170803
    [4] Hirsch L, Jette N, Frolkis A, Steeves T, Pringsheim T. 2016. The incidence of Parkinson's disease: a systematic review and meta-analysis. Neuroepidemiology, 46(4): 292−300. doi: 10.1159/000445751
    [5] Li H, Su LY, Yang LX, Li M, Liu QJ, Li ZH, et al. 2020. A cynomolgus monkey with naturally occurring Parkinson's disease. National Science Review: nwaa292. doi: 10.1093/nsr/nwaa292.
    [6] Luo X, Li M, Su B. 2016. Application of the genome editing tool CRISPR/Cas9 in non-human primates. Zoological Research, 37(4): 214−219.
    [7] Niu YY, Shen B, Cui YQ, Chen YC, Wang JY, Wang L, et al. 2014. Generation of gene-modified cynomolgus monkey via Cas9/RNA-mediated gene targeting in one-cell embryos. Cell, 156(4): 836−843. doi: 10.1016/j.cell.2014.01.027
    [8] Phillips KA, Bales KL, Capitanio JP, Conley A, Czoty PW, 't Hart BA, et al. 2014. Why primate models matter. American Journal of Primatology, 76(9): 801−827. doi: 10.1002/ajp.22281
    [9] Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, et al. 2017. Parkinson disease. Nature Reviews Disease Primers, 3: 17013. doi: 10.1038/nrdp.2017.13
    [10] Roth GS, Mattison JA, Ottinger MA, Chachich ME, Lane MA, Ingram DK. 2004. Aging in rhesus monkeys: relevance to human health interventions. Science, 305(5689): 1423−1426. doi: 10.1126/science.1102541
    [11] Tigges J, Gordon TP, McClure HM, Hall EC, Peters A. 1988. Survival rate and life span of rhesus monkeys at the Yerkes regional primate research center. American Journal of Primatology, 15(3): 263−273. doi: 10.1002/ajp.1350150308
    [12] Yan GM, Zhang GJ, Fang XD, Zhang YF, Li C, Ling F, et al. 2011. Genome sequencing and comparison of two nonhuman primate animal models, the cynomolgus and Chinese rhesus macaques. Nature Biotechnology, 29(11): 1019−1023. doi: 10.1038/nbt.1992
    [13] Zhao JG, Lai LX, Ji WZ, Zhou Q. 2019. Genome editing in large animals: current status and future prospects. National Science Review, 6(3): 402−420. doi: 10.1093/nsr/nwz013
    [14] Zimprich A, Biskup S, Leitner P, Lichtner P, Farrer M, Lincoln S, et al. 2004. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron, 44(4): 601−607. doi: 10.1016/j.neuron.2004.11.005
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出版历程
  • 收稿日期:  2021-01-07
  • 录用日期:  2021-02-08
  • 网络出版日期:  2021-02-08
  • 刊出日期:  2021-03-18

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