The Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Lab of Sichuan Province, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan 646000,China.
Division of Vascular Surgery, The Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, Sichuan 646000, China.
Gene. 2019 Sep 25;714:143996. doi: 10.1016/j.gene.2019.143996. Epub 2019 Jul 23.
The uniquely human α7-nAChR gene (CHRFAM7A) is evolved from the fusion of two partially duplicated genes, FAM7 and α7-nAChR gene (CHRNA7), and is inserted on same chromosome 15, 5' end of the CHRNA7 gene. Transcription of CHRFAM7A gene produces a 1256-bp open reading frame encoding dup-α7-nAChR, where a 27-aminoacid residues from FAM7 replaced the 146-aminoacid residues of the N-terminal extracellular ligand binding domain of α7-nAChR. In vitro, dup-α7-nAChR has been shown to form hetero-pentamer with α7-nAChR and dominant-negatively regulates the channel functions of α7-nAChR. However, the contribution of CHRFAM7A gene to the biology of α7-nAChR in the brain in vivo remains largely a matter of conjecture. CHRFAM7A transgenic mouse was created and differentially expressed proteins were profiled from the whole brain using iTRAQ-2D-LC-MS/MS proteomic technology. Proteins with a fold change of ≥1.2 or ≤0.83 and p < 0.05 were considered to be significant. Bioinformatics analysis showed that over-expression of the CHRFAM7A gene significantly modulated the proteins commonly involved in the signaling pathways of α7-nAChR-mediated neuropsychiatric disorders including Parkinson's disease, Alzheimer's disease, Huntington's disease, and alcoholism, suggesting that the CHRFAM7A gene contributes to the pathogenesis of neuropsychiatric disorders mostly likely through fine-tuning the functions of α7-nAChR in the brain.
人类特有的α7-nAChR 基因（CHRFAM7A）是由两个部分重复的基因 FAM7 和α7-nAChR 基因（CHRNA7）融合而成，并插入到相同的染色体 15 上，位于 CHRNA7 基因的 5'端。CHRFAM7A 基因的转录产生一个 1256 个碱基对的开放阅读框，编码 dup-α7-nAChR，其中 FAM7 的 27 个氨基酸残基取代了α7-nAChR 胞外配体结合域 N 端的 146 个氨基酸残基。体外研究表明，dup-α7-nAChR 与α7-nAChR 形成异源五聚体，并对α7-nAChR 的通道功能产生显性负调控作用。然而，CHRFAM7A 基因在体内对α7-nAChR 生物学的贡献在很大程度上仍是推测。创建了 CHRFAM7A 转基因小鼠，并使用 iTRAQ-2D-LC-MS/MS 蛋白质组学技术对整个大脑的差异表达蛋白进行了分析。折叠变化≥1.2 或≤0.83 且 p<0.05 的蛋白被认为是显著的。生物信息学分析表明，CHRFAM7A 基因的过表达显著调节了与 α7-nAChR 介导的神经精神疾病（包括帕金森病、阿尔茨海默病、亨廷顿病和酒精中毒）信号通路常见的蛋白质，表明 CHRFAM7A 基因很可能通过精细调节大脑中α7-nAChR 的功能来参与神经精神疾病的发病机制。
