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  2. Ablation of EYS in zebrafish causes mislocalisation of outer segment proteins, F-actin disruption and cone-rod dystrophy

Ablation of EYS in zebrafish causes mislocalisation of outer segment proteins, F-actin disruption and cone-rod dystrophy

  • Sci Rep. 2017 Apr 5;7:46098. doi: 10.1038/srep46098.
Zhaojing Lu 1 Xuebin Hu 1 Fei Liu 1 Dinesh C Soares 2 Xiliang Liu 1 Shanshan Yu 1 Meng Gao 1 Shanshan Han 1 Yayun Qin 1 Chang Li 1 Tao Jiang 1 Daji Luo 3 An-Yuan Guo 4 Zhaohui Tang 1 Mugen Liu 1
Affiliations

Affiliations

  • 1 Key Laboratory of Molecular Biophysics of Ministry of Education, Department of Genetics and Developmental Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, P.R China.
  • 2 MRC Human Genetics Unit/Centre for Genomic &Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, United Kingdom.
  • 3 Department of Medical Genetics, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, P.R China.
  • 4 Department of Bioinformatics and Systems Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, P.R China.
Abstract

Mutations in EYS are associated with autosomal recessive retinitis pigmentosa (arRP) and autosomal recessive cone-rod dystrophy (arCRD) however, the function of EYS and the molecular mechanisms of how these mutations cause retinal degeneration are still unclear. Because EYS is absent in mouse and rat, and the structure of the retina differs substantially between humans and Drosophila, we utilised zebrafish as a model organism to study the function of EYS in the retina. We constructed an EYS-knockout zebrafish-line by TALEN technology which showed visual impairment at an early age, while the histological and immunofluorescence assays indicated the presence of progressive retinal degeneration with a cone predominately affected pattern. These phenotypes recapitulate the clinical manifestations of arCRD patients. Furthermore, the EYS-/- zebrafish also showed mislocalisation of certain outer segment proteins (rhodopsin, opn1lw, opn1sw1, GNB3 and PRPH2), and disruption of actin filaments in photoreceptors. Protein mislocalisation may, therefore, disrupt the function of cones and rods in these zebrafish and cause photoreceptor death. Collectively, these results point to a novel role for EYS in maintaining the morphological structure of F-actin and in protein transport, loss of this function might be the trigger for the resultant cellular events that ultimately lead to photoreceptor death.

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