title: Ablation of EYS in zebrafish causes mislocalisation of outer segment proteins, F-actin disruption and cone-rod dystrophy.
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.
authors.affiliation: 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.
authors.forename: Zhaojing
authors.initials: Z
authors.lastname: Lu
authors.affiliation: 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.
authors.forename: Xuebin
authors.initials: X
authors.lastname: Hu
authors.affiliation: 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.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: MRC Human Genetics Unit/Centre for Genomic &Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, United Kingdom.
authors.forename: Dinesh C
authors.initials: DC
authors.lastname: Soares
authors.affiliation: 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.
authors.forename: Xiliang
authors.initials: X
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Yu
authors.affiliation: 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.
authors.forename: Meng
authors.initials: M
authors.lastname: Gao
authors.affiliation: 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.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Han
authors.affiliation: 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.
authors.forename: Yayun
authors.initials: Y
authors.lastname: Qin
authors.affiliation: 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.
authors.forename: Chang
authors.initials: C
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Medical Genetics, School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, P.R China.
authors.forename: Daji
authors.initials: D
authors.lastname: Luo
authors.affiliation: Department of Bioinformatics and Systems Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, P.R China.
authors.forename: An-Yuan
authors.initials: AY
authors.lastname: Guo
authors.affiliation: 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.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Tang
authors.affiliation: 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.
authors.forename: Mugen
authors.initials: M
authors.lastname: Liu
mesh_terms: D000199:Actins / Q000378:metabolism*; D000375:Aging / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D000071700:Cone-Rod Dystrophies / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004596:Electroretinography; D005136:Eye Proteins / Q000378:metabolism*; D017353:Gene Deletion; D055786:Gene Knockout Techniques; D055537:Light Signal Transduction; D012374:Rod Cell Outer Segment / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D000069896:Transcription Activator-Like Effector Nucleases / Q000378:metabolism; D014785:Vision, Ocular; D015027:Zebrafish / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D000199:Actins; C000629134:EYS protein, zebrafish; D005136:Eye Proteins; D029961:Zebrafish Proteins; D000069896:Transcription Activator-Like Effector Nucleases