关于RBFOX1和工作记忆:从基因组到转录组揭示了与注意力缺陷/过度活动障碍分开的转录后机制
Yuanxin Zhong1, Na Zhang2,3, Feng Zhao2
1Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health, National Clinical Research Center for Mental Disorders, Beijing, China.
Biological psychiatry global open science
|October 26, 2023
概括
基因分析发现了一种新的基因,RBFOX1,与工作记忆 (WM) 缺陷有关. 这种基因影响斑马鱼的突触功能,为患有WM障碍的精神疾病提供了洞察力.
科学领域:
- 神经遗传学 神经遗传学
- 精神病学遗传学 精神病学遗传学
- 分子生物学分子生物学
背景情况:
- 工作记忆 (WM) 缺陷在许多精神疾病中很常见.
- WM 损伤的遗传基础在很大程度上是未知的.
- 这项研究使用ADHD队列和斑马鱼模型调查了WM缺陷的遗传基础.
研究的目的:
- 识别与工作记忆障碍相关的遗传因素.
- 探索WM缺陷背后的生物机制.
- 在模型生物体中验证发现.
主要方法:
- 在两个大型注意力缺陷/多动症 (ADHD) 队列中进行协会分析.
- 使用生物信息分析和染色体相互作用数据进行功能性探索.
- 在斑马鱼模型中验证候选基因的基因操纵.
主要成果:
- 一个特定的位点 (rs75885813) 与WM缺陷显著相关,独立于ADHD诊断.
- 鉴定的单核酸多态可能通过染色体相互作用调节RBFOX1基因表达.
- 在斑马鱼中,对rbfox1的淘汰或基因组编辑导致了WM损伤而没有过度活跃.
- 在转录后水平上,RBFOX1调节了突触基因snap25a的表达,影响WM.
结论:
- 在RBFOX1中包含rs75885813的位置与工作记忆有关.
- 通过涉及snap25a的转录后机制,RBFOX1在突触可塑性和WM调节中发挥作用.
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