《生命科学》 2020, 32(12): 1365-1373

Shank3基因突变鼠行为及脑内机制变化研究进展

徐　丹¹ , 李晗冉^1,2 , 章志豪¹ , 孟昀晨¹ , 任炳瑞¹ , 张　嵘^3,4,5,* , 甄志平^1,*

¹北京师范大学体育与运动学院，北京 100875 ²澳门大学健康科学学院， 澳门特别行政区 999078 ³北京大学神经科学研究所，北京 100191 ⁴北京大学基础医学院神经生物学系，北京 100191 ⁵北京大学医学部孤独症研究中心，北京 100191

摘　要：

Shank3基因可编码多结构域SHANK3蛋白，该蛋白是兴奋性突触后致密区的支架蛋白，其不同结构域可供各种离子通道、受体和细胞内骨架直接或间接锚定，形成突触后重要的功能复合体。Shank3基因在神经系统分布较多，对维持神经元突触可塑性有重要作用。近年来，Shank3基因的突变被发现与多种神经发育障碍性疾病密切相关。不少实验室开始通过基因编辑技术构建基于Shank3基因突变的转基因鼠类模型，以研究该基因突变引起的疾病的机制问题，探究疾病的可能治疗方法。该文通过文献查阅，对基于Shank3基因突变的转基因鼠造成的异常行为及脑机制进行综述，探究该基因突变在神经疾病机制研究中的重要意义，为后续Shank3基因模式动物的深入研究做铺垫。

通讯作者：张　嵘 , Email:zhangrong@bjmu.edu.cn 甄志平 , Email:zzpxt@bnu.edu.cn

Advances in research on behavioral and brain mechanism changes of Shank3 mutant mice

XU Dan¹ , LI Han-Ran^1,2 , ZHANG Zhi-Hao¹ , MENG Yun-Chen¹ , REN Bing-Rui¹ , ZHANG Rong^3,4,5,* , ZHEN Zhi-Ping^1,*

¹College of P.E and Sports, Beijing Normal University, Beijing 100875, China ²Faculty of Healthy Sciences, University of Macau, Macau SAR 999078, China ³Neuroscience Research Institute, Peking University, Beijing 100191, China ⁴Institute of Neuroscience, Peking University, Beijing 100191, China ⁵Autism Research of Peking University Health Science Center, Beijing 100191, China

Abstract:

Shank3 gene encodes the multi-domain SHANK3 protein, which relates to a variety of scaffolding proteins to form functional complexes. It is widely distributed in the nervous system and plays an important role in maintaining synaptic plasticity of neurons. In recent years, studies have found that the mutation of Shank3 gene is significantly associated with a variety of neurodevelopmental disorders. Many laboratories have started to construct model animals through gene editing technology in order to study the mechanism of Shank3-related diseases and explore possible treatments. This article reviewed the behavior and brain mechanism of Shank3 mutant mice/rats, explored the significance of its mutation in the mechanism research of neurological diseases, laying a foundation for further research on Shank3 gene model animals.

Communication Author：ZHANG Rong , Email:zhangrong@bjmu.edu.cn ZHEN Zhi-Ping , Email:zzpxt@bnu.edu.cn