Zhang Hongsheng, Kang Eunchai, Wang Yaqing, Yang Chaojuan, Yu Hui, Wang Qin, Chen Zheyu, Zhang Chen, Christian Kimberly M, Song Hongjun, Ming Guo-Li, Xu Zhiheng
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Nat Commun. 2016 Jun 1;7:11773. doi: 10.1038/ncomms11773.
Several genome- and proteome-wide studies have associated transcription and translation changes of CRMP2 (collapsing response mediator protein 2) with psychiatric disorders, yet little is known about its function in the developing or adult mammalian brain in vivo. Here we show that brain-specific Crmp2 knockout (cKO) mice display molecular, cellular, structural and behavioural deficits, many of which are reminiscent of neural features and symptoms associated with schizophrenia. cKO mice exhibit enlarged ventricles and impaired social behaviour, locomotor activity, and learning and memory. Loss of Crmp2 in the hippocampus leads to reduced long-term potentiation, abnormal NMDA receptor composition, aberrant dendrite development and defective synapse formation in CA1 neurons. Furthermore, knockdown of crmp2 specifically in newborn neurons results in stage-dependent defects in their development during adult hippocampal neurogenesis. Our findings reveal a critical role for CRMP2 in neuronal plasticity, neural function and behavioural modulation in mice.
多项全基因组和蛋白质组研究已将CRMP2（塌陷反应调节蛋白2）的转录和翻译变化与精神疾病联系起来，但对于其在发育中的或成年哺乳动物大脑中的体内功能却知之甚少。在此我们表明，脑特异性Crmp2基因敲除（cKO）小鼠表现出分子、细胞、结构和行为缺陷，其中许多缺陷让人联想到与精神分裂症相关的神经特征和症状。cKO小鼠脑室扩大，社交行为、运动活动以及学习和记忆受损。海马体中Crmp2的缺失导致长时程增强减弱、NMDA受体组成异常、树突发育异常以及CA1神经元中突触形成缺陷。此外，在新生神经元中特异性敲低crmp2会导致其在成年海马神经发生过程中的发育出现阶段依赖性缺陷。我们的研究结果揭示了CRMP2在小鼠神经元可塑性、神经功能和行为调节中的关键作用。
