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丰富的神经环状RNA Cdr1as对视网膜维持并非不可或缺。

Abundant Neural circRNA Cdr1as Is Not Indispensable for Retina Maintenance.

作者信息

Chen Xue-Jiao, Li Meng-Lan, Wang Ya-Han, Mou Hao, Wu Zhen, Bao Siqi, Xu Ze-Hua, Zhang Hang, Wang Xiao-Yun, Zhang Chang-Jun, Xue Xiangyang, Jin Zi-Bing

机构信息

School of Ophthalmology and Optometry and Eye Hospital, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou, China.

School of Basic Medical Science, Wenzhou Medical University, Wenzhou, China.

出版信息

Front Cell Dev Biol. 2020 Nov 6;8:565543. doi: 10.3389/fcell.2020.565543. eCollection 2020.

Abstract

Cdr1as is the abundant circular RNA (circRNA) in human and vertebrate retinas. However, the role of Cdr1as in the retina remains unknown. In this study, we aimed to generate a Cdr1as knockout (KO) mouse model and investigate the retinal consequences of Cdr1as loss of function. Through hybridization (ISH), we demonstrated that Cdr1as is mainly expressed in the inner retina. Using CRISPR/Cas9 targeting Cdr1as, we successfully generated KO mice. We carried out ocular examinations in the KO mice until postnatal day 500. Compared with the age-matched wild-type (WT) siblings, the KO mice displayed increased b-wave amplitude of photopic electrophysiological response and reduced vision contrast sensitivity. Through small RNA profiling of the retinas, we determined that miR-7 was downregulated, while its target genes were upregulated. Taken together, our results demonstrated for the first time that Cdr1as ablation led to a mild retinal consequence in mice, indicating that Cdr1as abundance is not indispensable for retinal development and maintenance.

摘要

Cdr1as是人和脊椎动物视网膜中含量丰富的环状RNA(circRNA)。然而,Cdr1as在视网膜中的作用尚不清楚。在本研究中,我们旨在构建Cdr1as基因敲除(KO)小鼠模型,并研究Cdr1as功能丧失对视网膜的影响。通过原位杂交(ISH),我们证明Cdr1as主要在内层视网膜表达。利用靶向Cdr1as的CRISPR/Cas9技术,我们成功构建了基因敲除小鼠。我们对基因敲除小鼠进行了眼科检查,直至出生后500天。与年龄匹配的野生型(WT)同窝小鼠相比,基因敲除小鼠明视电生理反应的b波振幅增加,视觉对比敏感度降低。通过对视网膜进行小RNA分析,我们发现miR-7表达下调,而其靶基因表达上调。综上所述,我们的结果首次证明Cdr1as基因敲除会导致小鼠出现轻微的视网膜病变,表明Cdr1as的丰度对于视网膜的发育和维持并非不可或缺。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e6d/7677238/21abd9f9cdb0/fcell-08-565543-g001.jpg

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