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

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.