Macaque monkeys as a non-human primate circadian model.
Macaque monkeys as a non-human primate circadian model.
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DOI：
10.1093/nsr/nwz020
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发表时间：
2019-03
影响因子：
20.6
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Wang H
2017年诺贝尔生理学或医学奖授予了该领域的三位先驱，证明了昼夜节律研究已成为生物学中享有盛声望的领域之一。尽管诺贝尔奖表彰的是生物令人着迷的计时机制背后的分子遗传学基础的发现，但它确实强调了昼夜节律原理的深远医学意义。大量流行病学调查和动物模型研究表明，昼夜节律失调会导致身体功能失调和疾病，如睡眠障碍、代谢疾病、心血管疾病、免疫疾病和肿瘤、出生缺陷和生殖问题，以及神经和精神疾病[2,3]。然而，对于昼夜节律系统如何影响这些疾病，以及昼夜节律调节成分与导致这些疾病的途径之间的分子遗传联系，人们知之甚少。对这些疾病的昼夜节律调节的良好理解有望为其预防、诊断和治疗提供更好的方法，作为个性化/精准医学不可或缺的一部分。可能是由于它们的夜行性，这些疾病的许多啮齿动物的昼夜节律模型无法概括其相应的人类疾病的全部临床症状，特别是神经和精神疾病。因此，迫切需要开发在生理、代谢和行为方面与人类高度相似的昼行动物模型。在这方面，食蟹猴（Macaca fascicularis）作为一种非人灵长类动物具有很大的优势，特别是转基因、基因组编辑和体细胞克隆技术已经为其建立起来[4-6]。在这两篇发表于NSR第6卷第1期的研究中，张鸿春实验室与刘震组和孙强组合作，利用CRISPR-Cas9[7]成功建立了昼夜节律关键成分BMAL1的敲除了（KO）猕猴模型，随后通过体细胞核移植（SCNT）[8]克隆了BMAL1修饰的食蟹猴。Qiu等人将两个靶向BMAL1外显子13的gRNA和一个靶向BMAL1外显子8的gRNA微注射到吃蟹猴受精卵中，将88个微注射的胚胎移植到31只代理受体猴体内，获得了8只健康活产和2只自然流产的胎儿[7]。随后的基因分型鉴定出2只BMAL1 KO雄猴和1只BMAL1 KO雌猴，以及2只BMAL1 KO死猴[7]。正如预期的那样，BMAL1在这些ebmal1ko猴子的血细胞中表达被消除，其蛋白在血液中检测不到
Circadian studies have become one of the prestigious fields in biology, as evidenced by the award of 2017 Nobel Prize in Physiology or Medicine to three pioneers in this field [1]. Even though this Nobel Prize honored the discovery of the molecular genetic basis underlying the fascinating time-keeping mechanisms of living things, it indeed underscored the far-reaching medical implications of the circadian principle. Numerous epidemiological investigations as well as animal model studies revealed that circadian misalignment leads to malfunctions of the body and diseases such as sleep disorders, metabolic diseases, cardiovascular diseases, immune diseases and tumors, birth defects and reproductive problems, and neural and psychiatric diseases [2, 3]. However, very little is known about how the circadian system affects these diseases or molecular genetic links between the circadian regulatory components and the pathways leading to them. A good understanding of circadian regulation of these diseases promises to provide better approaches to their prevention, diagnosis and treatment, as an indispensable part of personalized/precision medicine. Probably due to their nocturnal natures, many rodent circadian models of these diseases fail to recapitulate the full spectrum of the clinical symptoms of their corresponding human diseases, particularly neural and psychiatric diseases. Hence, there is a pressing need to develop diurnal animal models that share high similarities in physiology, metabolism and behaviors with humans. In this regard, the cynomolgus monkey (Macaca fascicularis), a non-human primate, offers great advantages—especially the transgenic, genome-editing and somatic cell-cloning techniques have already been established for it [4–6]. In these two studies published in NSR Volume 6, Issue 1, the Hung-Chun Chang laboratory teamed up with the Zhen Liu group, and the Qiang Sun group, who recently reported cloning of the cynomolgus monkey with fetal fibroblast cells [5], successfully established the knockout (KO) macaque model for BMAL1, a key circadian component, using CRISPR-Cas9 [7] and subsequently cloned the BMAL1-modified cynomolgus monkey via somatic cell nuclear transfer (SCNT)[8].Qiu et al. microinjected two gRNAs targeting exon 13 and one gRNA targeting exon 8 of BMAL1 into cynomolgus monkey zygotes, transferred 88 microinjected embryos into 31 surrogate recipient monkeys and obtained 8 healthy live births and 2 spontaneously aborted fetuses [7]. Subsequent genotyping identified two BMAL1 KO male monkeys and one BMAL1 KO female monkey as well as two BMAL1 KO dead monkeys [7]. As expected, BMAL1 expression is abolished in blood cells of theseBMAL1KO monkeys and its protein is not detectable in
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影响因子：
20.6
作者：
Liu Z;Cai Y;Liao Z;Xu Y;Wang Y;Wang Z;Jiang X;Li Y;Lu Y;Nie Y;Zhang X;Li C;Bian X;Poo MM;Chang HC;Sun Q
通讯作者：
Sun Q
影响因子：
64.5
作者：
Niu, Yuyu;Shen, Bin;Sha, Jiahao
通讯作者：
Sha, Jiahao
过度表达 MeCP2 的转基因猴中的自闭症样行为和种系传播。
影响因子：
64.8
作者：
Liu, Zhen;Li, Xiao;Qiu, Zilong
通讯作者：
Qiu, Zilong
影响因子：
64.5
作者：
Liu, Zhen;Cai, Yijun;Sun, Qiang
通讯作者：
Sun, Qiang
BMAL1 基因敲除猕猴表现出睡眠减少和精神疾病
影响因子：
20.6
作者：
Qiu P;Jiang J;Liu Z;Cai Y;Huang T;Wang Y;Liu Q;Nie Y;Liu F;Cheng J;Li Q;Tang YC;Poo MM;Sun Q;Chang HC
通讯作者：
Chang HC