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Myelin regulatory factor deficiency is associated with the retinal photoreceptor defects in mice

Published online by Cambridge University Press:  03 May 2021

Xiaowei Yu
Affiliation:
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
Nannan Sun
Affiliation:
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
Xue Yang
Affiliation:
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
Zhenni Zhao
Affiliation:
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
Jiamin Zhang
Affiliation:
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
Miao Zhang
Affiliation:
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
Dandan Zhang
Affiliation:
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
Jian Ge*
Affiliation:
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
Zhigang Fan*
Affiliation:
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Sciences Key Laboratory, Beijing, China
*
Jian Ge, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, No. 7, Jinsui Road, Guangzhou, 510060, China. Email: gejian@mail.sysu.edu.cn
Address correspondence to: Zhigang Fan, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, No. 7, Jinsui Road, Guangzhou510060, China. Email: fanzhigang@mail.ccmu.edu.cn

Abstract

Previously, we reported the myelin regulatory factor (MYRF) as a candidate gene for nanophthalmos. We have also produced Myrf knockdown (Myrf+/−) mouse strain to investigate the cellular and molecular phenotypes of reduced MYRF expression in the retina. Myrf+/− mouse strain was generated using the CRISPR/Cas9 system. Optomotor response system, electroretinogram (ERG), spectral-domain optical coherence tomography (SD-OCT), histology, and immunohistochemistry were performed to evaluate retinal spatial vision, electrophysiological function, retinal thickness, and pathological changes in cone or rod photoreceptors, respectively. RNA sequencing (RNA-seq) was performed to investigate the underlying molecular mechanism linking Myrf deficiency with photoreceptor defects. The genotype and phenotype of CRISPR/Cas9-induced Myrf+/− mice and their offspring were comprehensively investigated. Photoreceptor defects were detected in the retinas of Myrf+/− mice. Visual acuity and ERG responses were decreased in Myrf+/− mice compared with the control mice (Myrf+/+). The loss of cone and rod neurons was proportional to the decreased outer nuclear layer (ONL) thickness. Moreover, RNA-seq revealed that phototransduction and estrogen signaling pathways played important roles in the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Myrf+/− mouse strain provides a good model to investigate the function of the MYRF gene. Photoreceptor defects with impaired functions of spatial vision and retinal electrophysiology indicate an important role played by MYRF in retinal development. Alterations in phototransduction and estrogen signaling pathways play important roles in linking Myrf deficiency with retinal photoreceptor defects.

Type
Research Article
Copyright
© The Author(s), 2021. Published by Cambridge University Press

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