Bi Yan, Chen Shiqing, Shen Qi, Guo Zhenming, Ren Decheng, Yuan Fan, Niu Weibo, Ji Lei, Liu Liangjie, Han Ke, Yu Tao, Yang Fengping, Wu Xi, Wang Lu, Li Xingwang, Yu Shunying, Xu Yifeng, He Lin, Shi Yi, Zhang Jing, Li Weidong, He Guang
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai, China.
Shanghai Key Laboratory of Psychotic Disorders, Brain Science and Technology Research Center, Shanghai Jiao Tong University, Shanghai, China.
Front Psychiatry. 2022 Apr 15;13:873873. doi: 10.3389/fpsyt.2022.873873. eCollection 2022.
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 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.
迪乔治综合征关键区域基因8（DGCR8）是微处理器复合体的关键组成部分，该复合体调控大多数微小RNA的成熟，其中一些微小RNA参与精神分裂症和神经发育过程。先前的研究发现，包含DGCR8的22q11.2位点会增加精神分裂症的发病风险。然而，DGCR8在精神分裂症及神经发育早期阶段中的作用尚不清楚。在本研究中，我们试图从人类样本和动物模型中确定DGCR8在精神分裂症中的作用。我们发现，DGCR8中rs3757的G等位基因和GG基因型会增加精神分裂症的发病风险，根据我们的双荧光素酶报告系统检测，这可能是由于DGCR8表达水平较高所致。利用过表达模型和成年小鼠，我们还发现，胚胎发育过程中Dgcr8异常增加会延迟神经元迁移，进而导致成年小鼠出现异常行为。综上所述，这些结果表明，DGCR8可能通过调节神经发育在精神分裂症的病因学中发挥作用。
