The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Curr Opin Psychiatry. 2021 Mar 1;34(2):87-93. doi: 10.1097/YCO.0000000000000675.
Genetic mutations in animals advance our understanding of disease mechanisms and treatments of neurodevelopmental disorders. Research with mutant mouse models is being extended to nonhuman primates whose brain development is closer to that of humans. This review summaries advances in mouse and nonhuman primate models.
Mutant mouse models recapitulate key symptoms in neurodevelopmental disorders. However, successful phenotypic reversal of symptoms in mouse models has not been replicated in human studies; this failure may be because of differences in the structure and physiology of the brain between rodents and humans. Rett syndrome MECP2 models and Phelan-McDermid syndrome where reduced expression of SH3 and multiple ankyrin repeat domains 3 (SHANK3) models have been introduced in nonhuman primates and are underway in other neurodevelopmental disorders.
Mutant mouse models in neurogenetic disorders continued to be pursued along with gene-edited and cell-based models in nonhuman primates. Established ethical guidelines are being followed and infrastructure being established to facilitate dissemination of primate transgenic models as they become available.
动物的基因突变促进了我们对神经发育障碍的发病机制和治疗方法的理解。对突变小鼠模型的研究正在扩展到与人类大脑发育更为接近的非人类灵长类动物。本综述总结了在小鼠和非人类灵长类动物模型方面的进展。
突变小鼠模型重现了神经发育障碍的关键症状。然而，在人类研究中未能复制出小鼠模型中症状的成功表型逆转；这种失败可能是由于啮齿动物和人类大脑的结构和生理学存在差异。雷特综合征 MECP2 模型和 Phelan-McDermid 综合征中 SH3 和多个锚蛋白重复结构域 3（SHANK3）表达减少的模型已在非人类灵长类动物中引入，并正在其他神经发育障碍中进行。
神经遗传疾病的突变小鼠模型仍在继续研究，同时也在非人类灵长类动物中进行基因编辑和基于细胞的模型研究。现有的伦理准则正在得到遵循，并且正在建立基础设施，以便在灵长类转基因模型可用时促进其传播。
