Knockout of zebrafish interleukin 7 receptor (IL7R) by the CRISPR/Cas9 system delays retinal neurodevelopment.
Knockout of zebrafish interleukin 7 receptor (IL7R) by the CRISPR/Cas9 system delays retinal neurodevelopment.
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CRISPR/Cas9 系统敲除斑马鱼白细胞介素 7 受体 (IL7R) 可延迟视网膜神经发育。
DOI：
10.1038/s41419-018-0337-z
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发表时间：
2018-02-15
影响因子：
9
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Cai S;Chen Y;Shang Y;Cui J;Li Z;Li Y
白介素7受体(IL7R)是一种跨膜受体，属于I型细胞因子受体家族，参与了多发性硬化症等神经退行性疾病的发病机制。靶向敲除il7r导致髓鞘形成延迟，突出了il7r在神经系统发育中的潜在作用。斑马鱼是研究神经发生的理想模型，而且其基因在斑马鱼和人类之间高度保守。本研究的目的是探讨il7rin神经发生的新功能。首先，利用规则间隔短回文重复序列相关9(CRISPR/CAS9)技术获得了−/−纯合子突变株系。其次，il7r−/−突变体的大体发育显示，眼睛明显变小，视网膜神经分化延迟。第三，微阵列分析显示，与光转导信号通路相关的基因在il7r−/−突变体中表达强烈下调。最后，行为学测试的结果表明，−/−突变幼虫的视觉功能受到了损害。总体而言，我们的数据表明，缺乏7-羟色胺会阻碍视网膜的发育。因此，il7是维持斑马鱼正常视网膜发育所必需的分子。
Interleukin 7 receptor(il7r), a transmembrane receptor, belongs to the type I cytokine receptor family.Il7ris involved in the pathogenesis of neurodegenerative disorders, such as multiple sclerosis. Targeted knockdown ofil7rleads to delayed myelination, highlighting the potential role ofil7rin the development of the nervous system. Zebrafish is an ideal model for the study of neurogenesis; moreover, theil7rgene is highly conserved between zebrafish and human. The aim of the present study was to investigate the novel function ofil7rin neurogenesis. First, anil7r−/−homozygous mutant line was generated by clustered regularly interspaced short palindromic repeats (CRISPR)-associated 9 (CRISPR/Cas9) technology. Second, the gross development ofil7r−/−mutants revealed remarkably smaller eyes and delayed retinal neurodifferentiation. Third, microarray analysis revealed that genes associated with the phototransduction signalling pathway were strongly down-regulated inil7r−/−mutants. Finally, the results from behavioural tests indicated that visual function was impaired inil7r−/−mutant larvae. Overall, our data demonstrate that a lack ofil7rretards the development of the retina. Thus,il7ris an essential molecule for maintaining normal retinal development in zebrafish.
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影响因子：
56.9
作者：
Jinek, Martin;Chylinski, Krzysztof;Charpentier, Emmanuelle
通讯作者：
Charpentier, Emmanuelle
影响因子：
46.9
作者：
通讯作者：
--
白细胞介素 7 受体 (IL-7R) 的下调会导致中枢神经系统脱髓鞘。
影响因子：
--
作者：
Lei X;Cai S;Chen Y;Cui J;Wang Y;Li Z;Li Y
通讯作者：
Li Y
影响因子：
5.4
作者：
Haas, Juergen;Korporal, Mirjam;Wildemann, Brigitte
通讯作者：
Wildemann, Brigitte
影响因子：
16.2
作者：
Kennedy, MJ;Lee, KA;Hurley, JB
通讯作者：
Hurley, JB