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.
Vis Neurosci. 2021 May 3;38:E005. doi: 10.1017/S0952523821000043.
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.
此前，我们报道了髓鞘调节因子（MYRF）是神经纤维瘤病的候选基因。我们还产生了 MYRF 敲低（Myrf+/-）小鼠品系，以研究视网膜中 MYRF 表达减少的细胞和分子表型。Myrf+/- 小鼠品系是使用 CRISPR/Cas9 系统产生的。通过视动反应系统、视网膜电图（ERG）、光谱域光学相干断层扫描（SD-OCT）、组织学和免疫组织化学分别评估视网膜空间视觉、电生理功能、视网膜厚度以及视锥或视杆光感受器的病理变化。进行 RNA 测序（RNA-seq）以研究将 MYRF 缺乏与光感受器缺陷联系起来的潜在分子机制。全面研究了 CRISPR/Cas9 诱导的 Myrf+/- 小鼠及其后代的基因型和表型。在 Myrf+/- 小鼠的视网膜中检测到光感受器缺陷。与对照小鼠（Myrf+/+）相比，Myrf+/- 小鼠的视力和 ERG 反应降低。锥体细胞和杆体细胞神经元的丢失与外核层（ONL）厚度的减少成正比。此外，RNA-seq 表明光转导和雌激素信号通路在京都基因与基因组百科全书（KEGG）分析中发挥重要作用。Myrf+/- 小鼠品系为研究 MYRF 基因的功能提供了良好的模型。具有空间视觉和视网膜电生理功能受损的光感受器缺陷表明 MYRF 在视网膜发育中起着重要作用。光转导和雌激素信号通路的改变在将 MYRF 缺乏与视网膜光感受器缺陷联系起来方面发挥着重要作用。
