MeCP2-PTEN调控神经干细胞增殖分化影响孤独症发生的分子机制

项目名称： MeCP2-PTEN调控神经干细胞增殖分化影响孤独症发生的分子机制

项目编号： No.91232712

项目类型： 重大研究计划

立项/批准年度： 2013

项目学科： 神经系统疾病、精神疾病

项目作者： 周文浩

作者单位： 复旦大学

项目金额： 60万元

中文摘要： 孤独症严重影响青少年情感和智力发育。既往在孤独症人群中发现MeCP2基因拷贝数增加，MeCP2基因突变小鼠具有孤独症表型，证实MeCP2参与孤独症的发生，但机制未明。PTEN参与神经干细胞增殖分化的调控，本课题组前期研究发现，抑制MeCP2降低PTEN表达，推测调控神经干细胞增殖分化可能是MeCP2参与孤独症发生的机制。本研究以中枢神经系统MeCP2和PTEN条件性敲除小鼠、MeCP2过表达小鼠为研究对象，采用体内和体外实验，1.确定MeCP2通过调控miR-137对PTEN表达的调节作用；2.研究MeCP2、miR-137与PTEN对神经干细胞增殖分化的影响；3.探索通过调控miR-137、PTEN水平是否能够改善孤独症小鼠模型的疾病表型。通过研究，从调控神经干细胞增殖分化的角度，阐明MeCP2、PTEN在孤独症发生中的作用，揭示MeCP2在孤独症发病中的机制，为孤独症干预提供新的思路。

中文关键词： MeCP2；瑞特综合征；孤独症；PTEN；

英文摘要： Autism seriously affects the normal emotional and intellectual development of adolescent. Previous studies showed that the copy number of MeCP2 gene was increased in the patients with autism. Moreover, mice with MeCP2 gene mutation had the characterization of autism. These data confirmed that MeCP2 have an important role in the occurrence and development of autism. However, the mechanism that MeCP2 affects autism is still unknown. PTEN regulate the proliferation and differentiation of neural stem cell. In our previous study, we found that inhibition MeCP2 decrease the expression of PTEN. So, we speculate that MeCP2 maybe play its role in the autism through the regulation of proliferation and differentiation of neural stem cell. In this study, the MeCP2 or PTEN conditional knockout mice and MeCP2 overexpression mice were used. The aims of the study are: 1. to clarify whether MeCP2 regulate the expression of PTEN by miR-137; 2. to observe the effects of MeCP2, miR137 and PTEN on proliferation and differentiation of neural stem cell; 3. to observe whether the regulation of miR137, PTEN improve the symptom of autism. In summary, our aim is to clarify the role and mechanism of MeCP2 and PTEN on occurrence and development of autism from the regulation of neural stem cell proliferation and differentiation. We hope to p

英文关键词： MeCP2；Rett syndrome；autism；PTEN；