Upregulation of DGCR8, a Candidate Predisposing to Schizophrenia in Han Chinese, Contributes to Phenotypic Deficits and Neuronal Migration Delay

DGCR8(一种易患汉族精神分裂症的候选基因)的上调导致表型缺陷和神经元迁移延迟

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作者:Yan Bi, Shiqing Chen, Qi Shen, Zhenming Guo, Decheng Ren, Fan Yuan, Weibo Niu, Lei Ji, Liangjie Liu, Ke Han, Tao Yu, Fengping Yang, Xi Wu, Lu Wang, Xingwang Li, Shunying Yu, Yifeng Xu, Lin He, Yi Shi, Jing Zhang, Weidong Li, Guang He

Abstract

DiGeorge Syndrome Critical Region Gene 8 (DGCR8) is a key component of the microprocessor complex governing the maturation of most microRNAs, some of which participate in schizophrenia and neural development. Previous studies have found that the 22q11.2 locus, containing DGCR8, confers a risk of schizophrenia. However, the role of DGCR8 in schizophrenia and the early stage of neural development has remained unknown. In the present study, we try to identify the role of DGCR8 in schizophrenia from human samples and animal models. We found that the G allele and GG genotype of rs3757 in DGCR8 conferred a higher risk of schizophrenia, which likely resulted from higher expression of DGCR8 according to our test of dual-luciferase reporter system. Employed overexpression model in utero and adult mice, we also revealed that the aberrant increase of Dgcr8 delayed neuronal migration during embryological development and consequently triggered abnormal behaviors in adult mice. Together, these results demonstrate that DGCR8 may play a role in the etiology of schizophrenia through regulating neural development.

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