Institute of Intelligent Robotics, Academy for Engineering and Technology, Fudan University, Shanghai, China; Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China.
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China.
Biochem Biophys Res Commun. 2023 Mar 12;648:28-35. doi: 10.1016/j.bbrc.2023.01.057. Epub 2023 Jan 20.
Methylated CpG binding protein 2 (MeCP2) plays an important role in the development and normal function of the neural system. Abnormally high expression of MECP2 leads to a subtype of autism called MECP2 duplication syndrome and MECP2 is considered one of the key pathogenic genes for autism spectrum disorders. However, the effect of MECP2 overexpression on neural activity is still not fully understood. Thus, transgenic (TG) animals that abnormally overexpress MeCP2 are important disease models in research on neurological function and autism. To create an animal model with a stronger and more stable autism phenotype, this study established a human MECP2 TG rat model and evaluated its movement ability, anxiety, and social behavior through behavioral tests. The results showed that MECP2 TG rats had an abnormally increased anxiety phenotype and social deficits in terms of abnormal social approach and social novelty preference, but no movement disorder. These autism-like behavioral phenotypes suggest that human MECP2 TG rats are suitable models for studying autism as they show more severe social deficit phenotypes and without interference from movement disorders affecting other phenotypes, which is an issue for mouse models with MECP2 duplication. In addition, this study performed preliminary exploration of the influence of the human MECP2 transgene on neural oscillation stability of the medial prefrontal cortex (mPFC), which is an important brain region for social interactions. Oscillation stability in MECP2 TG rats showed abnormal responses to social conditions. Overall, the results of this study provide a new research tool for understanding the mechanism of social impairment and treatment of autism. The results also provide evidence for the influence of MECP2 duplication on mPFC neural activity.
甲基化 CpG 结合蛋白 2（MeCP2）在神经系统的发育和正常功能中发挥着重要作用。MECP2 异常高表达导致一种称为 MECP2 重复综合征的自闭症亚型，并且 MECP2 被认为是自闭症谱系障碍的关键致病基因之一。然而，MECP2 过表达对神经活动的影响仍不完全清楚。因此，异常过表达 MeCP2 的转基因（TG）动物是研究神经功能和自闭症的重要疾病模型。为了创建具有更强和更稳定自闭症表型的动物模型，本研究构建了一种人 MECP2 TG 大鼠模型，并通过行为测试评估其运动能力、焦虑和社交行为。结果表明，MECP2 TG 大鼠表现出异常增加的焦虑表型和社交缺陷，表现在异常的社交接近和社交新颖性偏好方面，但没有运动障碍。这些自闭症样行为表型表明，人 MECP2 TG 大鼠是研究自闭症的合适模型，因为它们表现出更严重的社交缺陷表型，并且没有运动障碍干扰影响其他表型，这是 MECP2 重复的小鼠模型存在的问题。此外，本研究初步探索了人类 MECP2 转基因对内侧前额叶皮质（mPFC）神经振荡稳定性的影响，mPFC 是社交互动的重要脑区。MECP2 TG 大鼠的振荡稳定性对社交条件表现出异常反应。总的来说，本研究的结果为理解社交障碍和自闭症治疗机制提供了新的研究工具。研究结果还为 MECP2 重复对 mPFC 神经活动的影响提供了证据。
