Cloning of a gene-edited macaque monkey by somatic cell nuclear transfer

Liu, Zhen; Cai, Yijun; Liao, Zhaodi; Xu, Yuting; Wang, Yan; Wang, Zhanyang; Jiang, Xiaoyu; Li, Yunwei; Lu, Yong; Nie, Yanhong; Zhang, Xiaolin; Li, Chunyang; Bian, Xinyan; Poo, Mu‐ming; Chang, Hung-Chun; Sun, Qiang

doi:10.1093/nsr/nwz003

Cited by 64 publications

(54 citation statements)

References 27 publications

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“…Third, the electrophysiological analyses of rat brain with overexpression of BTN3A2 might not be a perfect system to show the neurobiological function of this gene as this gene was primate-specific [45]. Tests using non-human primates (NHPs) lacking BTN3A2 and/or overexpression of this gene should be a promising way to approach the final answer, given the recent advancements in genetic modification of NHPs [[73], [74], [75]].…”

Section: Discussionmentioning

confidence: 99%

Identification of the primate-specific gene BTN3A2 as an additional schizophrenia risk gene in the MHC loci

Zeng

et al. 2019

eBioMedicine

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Background: Schizophrenia is a complex mental disorder resulting in poor life quality and high social and economic burden. Despite the fact that genome-wide association studies (GWASs) have successfully identified a number of risk loci for schizophrenia, identifying the causal genes at the risk loci and elucidating their roles in disease pathogenesis remain major challenges. Methods: The summary data-based Mendelian randomization analysis (SMR) was used to integrate a large-scale GWAS of schizophrenia with brain expression quantitative trait loci (eQTL) data and brain methylation expression quantitative trait loci (meQTL) data, to identify novel risk gene(s) for schizophrenia. We then analyzed the mRNA expression and methylation statuses of the gene hit BTN3A2 during the early brain development. Electrophysiological analyses of CA1 pyramidal neurons were performed to evaluate the excitatory and inhibitory synaptic activity after overexpression of BTN3A2 in rat hippocampal slices. Cell surface binding assay was used to test the interaction of BTN3A2 and neurexins. Findings: We identified BTN3A2 as a potential risk gene for schizophrenia. The mRNA expression and methylation data showed that BTN3A2 expression in human brain is highest post-natally. Further electrophysiological analyses of rat hippocampal slices showed that BTN3A2 overexpression specifically suppressed the excitatory synaptic activity onto CA1 pyramidal neurons, most likely through its interaction with the presynaptic adhesion molecule neurexins. Interpretation: Increased expression of BTN3A2 might confer risk for schizophrenia by altering excitatory synaptic function. Our result constitutes a paradigm for distilling risk gene using an integrative analysis and functional characterization in the post-GWAS era.

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Section: Discussionmentioning

confidence: 99%

Identification of the primate-specific gene BTN3A2 as an additional schizophrenia risk gene in the MHC loci

Zeng

et al. 2019

eBioMedicine

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“…China has invested significantly in developing technologies in genome-editing in NHPs and has made dramatic progress in the past few years ( 93 – 102 ). The China Brain Project is expected to provide 15 y of generous funding to focus on the neurobiological basis of cognition and brain disorders with emphasis on the use of genetically modified macaque monkeys, clinical research, and application of artificial intelligence technologies ( 84 ).…”

Section: Resources and Infrastructure Required For Neuroscientific Stmentioning

confidence: 99%

Opportunities and limitations of genetically modified nonhuman primate models for neuroscience research

Feng

Jensen

Greely

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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The recently developed new genome-editing technologies, such as the CRISPR/Cas system, have opened the door for generating genetically modified nonhuman primate (NHP) models for basic neuroscience and brain disorders research. The complex circuit formation and experience-dependent refinement of the human brain are very difficult to model in vitro, and thus require use of in vivo whole-animal models. For many neurodevelopmental and psychiatric disorders, abnormal circuit formation and refinement might be at the center of their pathophysiology. Importantly, many of the critical circuits and regional cell populations implicated in higher human cognitive function and in many psychiatric disorders are not present in lower mammalian brains, while these analogous areas are replicated in NHP brains. Indeed, neuropsychiatric disorders represent a tremendous health and economic burden globally. The emerging field of genetically modified NHP models has the potential to transform our study of higher brain function and dramatically facilitate the development of effective treatment for human brain disorders. In this paper, we discuss the importance of developing such models, the infrastructure and training needed to maximize the impact of such models, and ethical standards required for using these models.

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“…In 2018, Liu et al, successfully obtained newborn baby macaques via somatic cell nuclear transfers (scnt) from fetal fibroblast cells [77]. Furthermore, cloned monkeys were generated via scnt of fibroblast cells from BMAL1 mutant monkeys [78]. These results suggest that targeted gene knockout/knockin NHP models may be produced via scnt of fibroblast cells carrying objective target gene knockout/knockin mutations.…”

Section: Future Perspectivesmentioning

confidence: 99%

Development of genetically modified nonhuman primates toward models for translational research

Sasaki

2019

Translational and Regulatory Sciences

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Since the genetic, metabolic, and physiological characteristics of nonhuman primates (NHPs) are very similar to those of humans, NHPs serve as excellent animal models for biomedical research. Recent advances in genetic engineering and assisted reproductive technologies related to NHPs have enabled the development of genetically modified NHP models for human disease related studies. The common marmoset (Callithrix jacchus) is a useful laboratory animal model that is suitable for generating genetically engineered models due to its unique reproductive characteristics, such as prolific breeding, relatively short gestation period and small body size. Genetically modified marmoset models may be used as critical intermediaries to accelerate the progression of various conceptual technologies and therapeutics from the basic research stage to the clinical application stage. The last decade has witnessed the growth of genetic engineering technologies pertaining to NHPs as well as new gene modification technologies, such as gene editing. Such technological advances have enabled the development of genetically engineered NHP disease models for translational research.

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Cloning of a gene-edited macaque monkey by somatic cell nuclear transfer

Cited by 64 publications

References 27 publications

Identification of the primate-specific gene BTN3A2 as an additional schizophrenia risk gene in the MHC loci

Identification of the primate-specific gene BTN3A2 as an additional schizophrenia risk gene in the MHC loci

Opportunities and limitations of genetically modified nonhuman primate models for neuroscience research

Development of genetically modified nonhuman primates toward models for translational research

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