Knockout of RP2 decreases GRK1 and rod transducin subunits and leads to photoreceptor degeneration in zebrafish.

Autor:	Liu F; 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, 1037 Luoyu Road, Wuhan, Hubei 430074, PR China., Chen J; 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, 1037 Luoyu Road, Wuhan, Hubei 430074, PR China., Yu S; 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, 1037 Luoyu Road, Wuhan, Hubei 430074, PR China., Raghupathy RK; Department of Life Sciences, Glasgow Caledonian University, Glasgow G4 0BA, UK and and., Liu X; 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, 1037 Luoyu Road, Wuhan, Hubei 430074, PR China., Qin Y; 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, 1037 Luoyu Road, Wuhan, Hubei 430074, PR China., Li C; 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, 1037 Luoyu Road, Wuhan, Hubei 430074, PR China., Huang M; 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, 1037 Luoyu Road, Wuhan, Hubei 430074, PR China., Liao S; 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, 1037 Luoyu Road, Wuhan, Hubei 430074, PR China., Wang J; 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, 1037 Luoyu Road, Wuhan, Hubei 430074, PR China., Zou J; Institute of Translational Medicine, Zhejiang University, 268 Kaixuan Road, Zhongxin Beilou, Hangzhou, 310029 Zhejiang, PR China., Shu X; Department of Life Sciences, Glasgow Caledonian University, Glasgow G4 0BA, UK and and., Tang Z; 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, 1037 Luoyu Road, Wuhan, Hubei 430074, PR China, lium@hust.edu.cn zh_tang@hust.edu.cn., Liu M; 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, 1037 Luoyu Road, Wuhan, Hubei 430074, PR China, lium@hust.edu.cn zh_tang@hust.edu.cn.
Jazyk:	angličtina
Zdroj:	Human molecular genetics [Hum Mol Genet] 2015 Aug 15; Vol. 24 (16), pp. 4648-59. Date of Electronic Publication: 2015 Jun 01.
DOI:	10.1093/hmg/ddv197
Abstrakt:	Retinitis pigmentosa (RP) affects about 1.8 million individuals worldwide. X-linked retinitis pigmentosa (XLRP) is one of the most severe forms of RP. Nearly 85% of XLRP cases are caused by mutations in the X-linked retinitis pigmentosa 2 (RP2) and RPGR. RP2 has been considered to be a GTPase activator protein for ARL3 and to play a role in the traffic of ciliary proteins. The mechanism of how RP2 mutations cause RP is still unclear. In this study, we generated an RP2 knockout zebrafish line using transcription activator-like effector nuclease technology. Progressive retinal degeneration could be observed in the mutant zebrafish. The degeneration of rods' outer segments (OSs) is predominant, followed by the degeneration of cones' OS. These phenotypes are similar to the characteristics of RP2 patients, and also partly consistent with the phenotypes of RP2 knockout mice and morpholino-mediated RP2 knockdown zebrafish. For the first time, we found RP2 deletion leads to decreased protein levels and abnormal retinal localizations of GRK1 and rod transducin subunits (GNAT1 and GNB1) in zebrafish. Furthermore, the distribution of the total farnesylated proteins in zebrafish retina is also affected by RP2 ablation. These molecular alterations observed in the RP2 knockout zebrafish might probably be responsible for the gradual loss of the photoreceptors' OSs. Our work identified the progression of retinal degeneration in RP2 knockout zebrafish, provided a foundation for revealing the pathogenesis of RP caused by RP2 mutations, and would help to develop potential therapeutics against RP in further studies. (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
Databáze:	MEDLINE
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