Extension of the Lifespan of a Mouse Model of Rett Syndrome by Intracerebroventricular Delivery of MECP2
Extension of the Lifespan of a Mouse Model of Rett Syndrome by Intracerebroventricular Delivery of MECP2
复制标题
通过脑室内输送 MECP2 延长 Rett 综合征小鼠模型的寿命
DOI：
10.1007/s12264-022-00974-y
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发表时间：
2022
影响因子：
5.6
通讯作者：
Z. Qiu
中科院分区：
文献类型：
--
作者：
Kan Yang;Cheng Cheng;Yiting Yuan;Yue;Shifang Shan;Z. Qiu
在这里，我们报告，通过将腺相关病毒血清型9-甲基CpG结合蛋白2（AAV 9-MECP 2），这是由人突触蛋白（hSyn）启动子或巨细胞病毒早期增强子/鸡β-肌动蛋白（CAG）启动子驱动，通过脑室内（ICV）注射到出生后第2天的侧脑室（LV），Mecp 2-/y小鼠的寿命明显延长。我们发现，MECP 2的蛋白水平在整个大脑的神经元中得到了部分拯救，包括皮层、海马和下丘脑。此外，与注射AAV 9-hSyn-MECP 2的小鼠相比，注射AAV 9-CAG-MECP 2的Mecp 2-/y小鼠在神经元中表现出更高的转导效率、更低的局部过表达风险和增加的寿命。重要的是，包括体重减轻、异常运动评分和异常步态评分的病理学特征在注射AAV 9-CAG-MECP 2的Mecp 2-/y小鼠中得到部分挽救。我们的研究结果为RTT的遗传干扰提供了一种新的方法。为了产生具有完全Mecp 2基因敲除的Mecp 2-/y小鼠，
Here, we report that, by delivering adeno-associated virus serotype 9–methyl CpG binding protein 2 (AAV9-MECP2), which was driven by the human synapsin (hSyn) promoter or the cytomegalovirus early enhancer/chicken β-actin (CAG) promoter, into the lateral ventricle (LV) by intracerebroventricular (ICV) injection on postnatal day 2, the lifespans of Mecp2 -/y mice were apparently extended. We found that the protein level of MECP2 was partially rescued in neurons throughout the brain, including the cortex, hippocampus, and hypothalamus. Besides, Mecp2 -/y mice injected with AAV9-CAG-MECP2 showed higher transduction efficiency in neurons, lower local overexpression risk, and increased lifespan compared with those injected with AAV9-hSyn-MECP2. Importantly, pathological features including reduced body weight, abnormal locomotor score, and abnormal gait score were partially rescued in Mecp2 -/y mice injected with AAV9-CAG-MECP2. Our results provide a novel approach for genetic interference in RTT. To generate Mecp2 -/y mice with complete Mecp2 gene knock-out
影响因子：
4.2
作者：
Gray, Steven J.;Foti, Stacey B.;Samulski, R. Jude
通讯作者：
Samulski, R. Jude
DOI：
10.1073/pnas.0401626101
发表时间：
2004-04-20
影响因子：
11.1
作者：
Luikenhuis, S;Giacometti, E;Jaenisch, R
通讯作者：
Jaenisch, R