Opportunities and limitations of genetically modified nonhuman primate models for neuroscience research.
Opportunities and limitations of genetically modified nonhuman primate models for neuroscience research.
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DOI：
10.1073/pnas.2006515117
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发表时间：
2020-09-29
影响因子：
11.1
通讯作者：
Morrison JH
中科院分区：
文献类型：
--
作者：
Feng G;Jensen FE;Greely HT;Okano H;Treue S;Roberts AC;Fox JG;Caddick S;Poo MM;Newsome WT;Morrison JH
最近开发的新的基因组编辑技术，如CRISPR/CAS系统，为产生基础神经科学和大脑疾病研究的转基因非人灵长类(NHP)模型打开了大门。人脑复杂的电路形成和依赖经验的精炼在体外很难建模，因此需要使用活体全动物模型。对于许多神经发育和精神障碍来说，异常的回路形成和完善可能是其病理生理学的中心。重要的是，许多与人类较高认知功能和许多精神疾病有关的关键回路和区域细胞群在低等哺乳动物的大脑中并不存在，而这些类似的区域在NHP大脑中复制。事实上，神经精神障碍在全球范围内代表着巨大的健康和经济负担。转基因NHP模型的新兴领域有可能改变我们对高级大脑功能的研究，并极大地促进人类大脑疾病有效治疗的发展。在本文中，我们讨论了开发此类模型的重要性、最大化此类模型的影响所需的基础设施和培训，以及使用这些模型所需的伦理标准。
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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