title: Early Parkinson's disease symptoms in α-synuclein transgenic monkeys.
abstract: Parkinson's disease (PD) is an age-dependent neurodegenerative disease that can be caused by genetic mutations in α-synuclein (α-syn) or duplication of wild-type α-syn; PD is characterized by the deposition of α-syn aggregates, indicating a gain of toxicity from accumulation of α-syn. Although the major neuropathologic feature of PD is the degeneration of dopaminergic (DA) neurons in the substantia nigra, non-motor symptoms including anxiety, cognitive defect and sleep disorder precede the onset of motor impairment, and many clinical symptoms of PD are not caused by degeneration of DA neurons. Non-human primate models of PD are important for revealing the early pathology in PD and identifying effective treatments. We established transgenic PD rhesus monkeys that express mutant α-syn (A53T). Six transgenic A53T monkeys were produced via lentiviral vector expressing A53T in fertilized monkey eggs and subsequent embryo transfer to surrogates. Transgenic A53T is expressed in the monkey brain and causes age-dependent non-motor symptoms, including cognitive defects and anxiety phenotype, without detectable sleeping disorders. The transgenic α-syn monkeys demonstrate the specific early symptoms caused by mutant α-syn and provide insight into treatment of early PD.
authors.affiliation: Yunnan Key Laboratory of Primate Biomedical Research, Kunming 650500, China, Kunming Biomed International and National Engineering Research Center of Biomedicine and Animal Science, Kunming 650500, China, Primate Translational Medicine Research Center, Kunming University of Science and Technology, Kunming, Yunnan, 650500, China.
authors.forename: Yuyu
authors.initials: Y
authors.lastname: Niu
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 10010, China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Guo
authors.affiliation: Yunnan Key Laboratory of Primate Biomedical Research, Kunming 650500, China, Kunming Biomed International and National Engineering Research Center of Biomedicine and Animal Science, Kunming 650500, China, Primate Translational Medicine Research Center, Kunming University of Science and Technology, Kunming, Yunnan, 650500, China.
authors.forename: Yongchang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Chuan-En
authors.initials: CE
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 10010, China.
authors.forename: Jinquan
authors.initials: J
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 10010, China.
authors.forename: Weili
authors.initials: W
authors.lastname: Yang
authors.affiliation: Yunnan Key Laboratory of Primate Biomedical Research, Kunming 650500, China, Kunming Biomed International and National Engineering Research Center of Biomedicine and Animal Science, Kunming 650500, China, Primate Translational Medicine Research Center, Kunming University of Science and Technology, Kunming, Yunnan, 650500, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Kang
authors.affiliation: Yunnan Key Laboratory of Primate Biomedical Research, Kunming 650500, China, Kunming Biomed International and National Engineering Research Center of Biomedicine and Animal Science, Kunming 650500, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Si
authors.affiliation: Yunnan Key Laboratory of Primate Biomedical Research, Kunming 650500, China, Kunming Biomed International and National Engineering Research Center of Biomedicine and Animal Science, Kunming 650500, China, Primate Translational Medicine Research Center, Kunming University of Science and Technology, Kunming, Yunnan, 650500, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Physiology, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan and.
authors.forename: Shang-Hsun
authors.initials: SH
authors.lastname: Yang
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Shihua
authors.initials: S
authors.lastname: Li
authors.affiliation: Yunnan Key Laboratory of Primate Biomedical Research, Kunming 650500, China, Kunming Biomed International and National Engineering Research Center of Biomedicine and Animal Science, Kunming 650500, China, Primate Translational Medicine Research Center, Kunming University of Science and Technology, Kunming, Yunnan, 650500, China xli2@emory.edu wji@kbimed.com.
authors.forename: Weizhi
authors.initials: W
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 10010, China, Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA, xli2@emory.edu wji@kbimed.com.
authors.forename: Xiao-Jiang
authors.initials: XJ
authors.lastname: Li
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000378:metabolism; D005260:Female; D006801:Humans; D008253:Macaca mulatta / Q000235:genetics / Q000378:metabolism; D008297:Male; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051844:alpha-Synuclein / Q000235:genetics* / Q000378:metabolism / Q000633:toxicity
chemical_list: D051844:alpha-Synuclein