Generation of Gene-Modified Cynomolgus Monkey via Cas9/RNA-Mediated Gene Targeting in One-Cell Embryos

Niu, Yuyu; Shen, Bin; Cui, Yiqiang; Chen, Yongchang; Wang, Jianying; Wang, Lei; Kang, Yu; Zhao, Xiaoyang; Si, Wei; Li, Wei; Xiang, Andy Peng; Zhou, Jianghua; Guo, Xuejiang; Bi, Ye; Si, Chenyang; Hu, Baishi; Dong, Guoying; Wang, Hong; Zhou, Zuomin; Li, Tianqing; Tan, Tao; Pu, Xiuqiong; Wang, Fang; Ji, Shaocheng; Zhou, Qi; Huang, Xingxu; Ji, Weizhi; Sha, Jiahao

doi:10.1016/j.cell.2014.01.027

Cited by 930 publications

(724 citation statements)

References 27 publications

(37 reference statements)

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“…An ethically more complicated potential use of CRISPR-Cas9 was underscored in February 2014, when researchers described how they had used it to make precise changes to the genomes of cynomolgus monkey embryos 7 . (Cynomolgus monkeys are so genetically close to humans that they are commonly used to model human genetic disease.)…”

Section: Growing Excitementmentioning

confidence: 99%

Genome-editing revolution: My whirlwind year with CRISPR

Doudna

2015

Nature

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Section: Growing Excitementmentioning

confidence: 99%

Genome-editing revolution: My whirlwind year with CRISPR

Doudna

2015

Nature

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“…It used to be quite diffi cult to perform genetic manipulation in monkeys, but at present, these techniques are rapidly developing in nonhuman primates [53,54] . Thus it will be possible to develop genetic monkey models for schizophrenia by genetic manipulation techniques in the near future.…”

Section: Possible Genetic Monkey Models Of Schizophrenia In the Near mentioning

confidence: 99%

“…Partial knockout of NRG1 in mice causes social interaction problems, reduced prepulse inhibition, and higher levels of spontaneous locomotion. These symptoms are reduced by clozapine [51] .It used to be quite diffi cult to perform genetic manipulation in monkeys, but at present, these techniques are rapidly developing in nonhuman primates [53,54] . Thus it will be possible to develop genetic monkey models for schizophrenia by genetic manipulation techniques in the near future.…”

mentioning

confidence: 99%

Prefrontal dysfunction and a monkey model of schizophrenia

et al. 2015

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The prefrontal cortex is implicated in cognitive functioning and schizophrenia. Prefrontal dysfunction is closely associated with the symptoms of schizophrenia. In addition to the features typical of schizophrenia, patients also present with aspects of cognitive disorders. Based on these relationships, a monkey model mimicking the cognitive symptoms of schizophrenia has been made using treatment with the non-specific competitive N-methyl-D-aspartate receptor antagonist, phencyclidine. The symptoms are ameliorated by atypical antipsychotic drugs such as clozapine. The benefi cial effects of clozapine on behavioral impairment might be a specifi c indicator of schizophrenia-related cognitive impairment. Keywords: prefrontal cortex; schizophrenia; monkey model ·Review· IntroductionOne percent of the adult population, particularly young adults, are affected by schizophrenia. Schizophrenic patients typically present with hallucinations, delusions, withdrawal from social activities, loss of personal care skills, and flat or inappropriate emotional responses to situations [1] . Although many factors have been associated with schizophrenia, including genetic factors, early environmental influences, and neurobiological, psychological, and sociological processes [2][3][4] that are very important contributory factors, the mechanism underlying this disorder is unknown. Patient data are insufficient for understanding the pathology and etiology of schizophrenia.Further, direct experimentation on human subjects is ethically unacceptable. Thus, animal models have become an indispensable tool for pathological research. Unlike other neurological diseases such as stroke, epilepsy, and Parkinson's disease that can be easily replicated in animals, some of the symptoms of schizophrenia human patients, such as thinking disorders, delusions, and hallucinations, are difficult to replicate in animals.For many years, there has been no appropriate nonhuman primate model of schizophrenia. In addition to the typical features of schizophrenia, patients present with aspects of prefrontal cognitive disorders involving, e.g., working memory, selective attention, initiating movement, and planning. Based on these relationships, a monkey model of schizophrenia could be developed by mimicking its cognitive symptoms. In this review, we introduce schizophrenia and the prefrontal cortex (PFC) as well as their relationship and discuss the development of a monkey model of schizophrenia, including the methods and behavioral tests of the model. The Prefrontal Cortex and SchizophreniaThe volume of the human brain is twice that of the chimpanzee, and the PFC, which is the most rostral component of the primate cortex, has expanded most in humans [5,6] . In other species, the PFC functions in voluntary motor control, whereas in primates, it has developed [5][6][7] . The PFC has broad connections with many parts of the brain, particularly the sub-regions of the limbic system [10] . The human PFC, which is better developed than in other primates, is the primary ...

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“…If the sequencing is time-consuming, researchers must develop a novel, efficient method based on genetic or epigenetic vestiges which are associated with genome editing technology. For instance, in a recent report on a primate modified via CRISPR/Cas-mediated gene targeting, the potential off-target sites were defined and comprehensively investigated in the primate genome [17]. Such an approach can be effective if a scientific and regulatory consensus is reached.…”

Section: Technical Aspectsmentioning

confidence: 99%