Schmid Ralf S, Tsujimoto Naomi, Qu Qiang, Lei Hong, Li En, Chen Taiping, Blaustein Cecile Spielewoy
Duke University, Center for Drug Discovery and Department of Neurobiology, Durham, NC, USA.
Neuroreport. 2008 Mar 5;19(4):393-8. doi: 10.1097/WNR.0b013e3282f5661c.
Rett syndrome, a pervasive X-linked neurodevelopmental disorder in young girls, is caused by loss-of-function mutations in the gene that encodes the transcriptional repressor methyl-CpG-binding protein 2 (MeCP2). Mecp2-knockout mice phenocopy the major symptoms found in human patients and have advanced our understanding of the function of MeCP2 and mechanism of Rett syndrome. To study the behavior of the MeCP2 protein in vivo, we have generated a knock-in reporter mouse model that expresses MeCP2-enhanced green fluorescent protein (EGFP) fusion protein instead of endogenous MeCP2. Here we show that expression of the fusion protein in the brain remarkably mirrors endogenous MeCP2 expression in all temporal and spatial aspects. This mouse model may be a valuable tool for studying Rett syndrome and for developing therapies.
雷特综合征是一种常见于年轻女孩的X连锁神经发育障碍疾病，由编码转录抑制因子甲基-CpG结合蛋白2（MeCP2）的基因功能丧失性突变引起。Mecp2基因敲除小鼠可模拟人类患者的主要症状，增进了我们对MeCP2功能及雷特综合征发病机制的理解。为了在体内研究MeCP2蛋白的行为，我们构建了一种敲入报告基因小鼠模型，该模型表达MeCP2-增强型绿色荧光蛋白（EGFP）融合蛋白而非内源性MeCP2。在此我们表明，该融合蛋白在大脑中的表达在所有时间和空间方面都显著反映了内源性MeCP2的表达。这种小鼠模型可能是研究雷特综合征和开发治疗方法的宝贵工具。
