PMID- 29449560 OWN - NLM STAT- MEDLINE DCOM- 20200406 LR - 20200408 IS - 2041-4889 (Electronic) VI - 9 IP - 3 DP - 2018 Feb 15 TI - Knockout of zebrafish interleukin 7 receptor (IL7R) by the CRISPR/Cas9 system delays retinal neurodevelopment. PG - 273 LID - 10.1038/s41419-018-0337-z [doi] LID - 273 AB - Interleukin 7 receptor (il7r), a transmembrane receptor, belongs to the type I cytokine receptor family. Il7r is involved in the pathogenesis of neurodegenerative disorders, such as multiple sclerosis. Targeted knockdown of il7r leads to delayed myelination, highlighting the potential role of il7r in the development of the nervous system. Zebrafish is an ideal model for the study of neurogenesis; moreover, the il7r gene is highly conserved between zebrafish and human. The aim of the present study was to investigate the novel function of il7r in neurogenesis. First, an il7r (-/-) homozygous mutant line was generated by clustered regularly interspaced short palindromic repeats (CRISPR)-associated 9 (CRISPR/Cas9) technology. Second, the gross development of il7r(-/-) 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 in il7r (-/-) mutants. Finally, the results from behavioural tests indicated that visual function was impaired in il7r (-/-) mutant larvae. Overall, our data demonstrate that a lack of il7r retards the development of the retina. Thus, il7r is an essential molecule for maintaining normal retinal development in zebrafish. FAU - Cai, Shijiao AU - Cai S AD - Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University School of Medicine, Tianjin, 300071, China. AD - State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, 300350, China. FAU - Chen, Yang AU - Chen Y AD - Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University School of Medicine, Tianjin, 300071, China. FAU - Shang, Yue AU - Shang Y AD - Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University School of Medicine, Tianjin, 300071, China. FAU - Cui, Jianlin AU - Cui J AD - Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University School of Medicine, Tianjin, 300071, China. AD - Medical International Collaborative Innovation Center, Nankai University, Tianjin, 300071, China. FAU - Li, Zongjin AU - Li Z AUID- ORCID: 0000-0002-4603-3743 AD - Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University School of Medicine, Tianjin, 300071, China. FAU - Li, Yuhao AU - Li Y AUID- ORCID: 0000-0003-2022-9526 AD - Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University School of Medicine, Tianjin, 300071, China. liyuhao@nankai.edu.cn. AD - Medical International Collaborative Innovation Center, Nankai University, Tianjin, 300071, China. liyuhao@nankai.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180215 PL - England TA - Cell Death Dis JT - Cell death & disease JID - 101524092 RN - 0 (Receptors, Interleukin-7) RN - 0 (Zebrafish Proteins) RN - EC 3.1.- (CRISPR-Associated Protein 9) SB - IM MH - Animals MH - Animals, Genetically Modified MH - CRISPR-Associated Protein 9/*genetics/metabolism MH - *CRISPR-Cas Systems MH - *Clustered Regularly Interspaced Short Palindromic Repeats MH - Gene Expression Regulation, Developmental MH - *Gene Knockdown Techniques MH - Mutation MH - *Neurogenesis MH - Photic Stimulation MH - Receptors, Interleukin-7/*deficiency/genetics MH - Retinal Neurons/*metabolism MH - Signal Transduction MH - Vision, Ocular MH - Zebrafish/embryology/genetics/*metabolism MH - Zebrafish Proteins/*deficiency/genetics PMC - PMC5833684 COIS- The authors declare that they have no conflict of interest. EDAT- 2018/02/17 06:00 MHDA- 2020/04/09 06:00 PMCR- 2018/02/15 CRDT- 2018/02/17 06:00 PHST- 2017/10/31 00:00 [received] PHST- 2018/01/22 00:00 [accepted] PHST- 2018/01/04 00:00 [revised] PHST- 2018/02/17 06:00 [entrez] PHST- 2018/02/17 06:00 [pubmed] PHST- 2020/04/09 06:00 [medline] PHST- 2018/02/15 00:00 [pmc-release] AID - 10.1038/s41419-018-0337-z [pii] AID - 337 [pii] AID - 10.1038/s41419-018-0337-z [doi] PST - epublish SO - Cell Death Dis. 2018 Feb 15;9(3):273. doi: 10.1038/s41419-018-0337-z.