Deletion of prominin-1 in mice results in disrupted photoreceptor outer segment protein homeostasis

Yu-Shu Xiao; Jian Liang; Min Gao; Jun-Ran Sun; Yang Liu; Jie-Qiong Chen; Xiao-Huan Zhao; Yi-Min Wang; Yu-Hong Chen; Yu-Wei Wang; Xiao-Ling Wan; Xue-Ting Luo; Xiao-Dong Sun

doi:10.18240/ijo.2021.09.07

International Journal of Ophthalmology (Sep 2021)

Deletion of prominin-1 in mice results in disrupted photoreceptor outer segment protein homeostasis

Yu-Shu Xiao,
Jian Liang,
Min Gao,
Jun-Ran Sun,
Yang Liu,
Jie-Qiong Chen,
Xiao-Huan Zhao,
Yi-Min Wang,
Yu-Hong Chen,
Yu-Wei Wang,
Xiao-Ling Wan,
Xue-Ting Luo,
Xiao-Dong Sun

Affiliations

Yu-Shu Xiao: Xiao-Dong Sun and Xue-Ting Luo. Department of Ophthalmology, Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, 100 Hai Ning Road, Shanghai 200080, China. [email protected]; [email protected]
Jian Liang: Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University, School of Medicine, Shanghai 200080, China; Shanghai Key Laboratory of Fundus Diseases, Shanghai 200080, China
Min Gao: Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University, School of Medicine, Shanghai 200080, China
Jun-Ran Sun: Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University, School of Medicine, Shanghai 200080, China
Yang Liu: Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University, School of Medicine, Shanghai 200080, China
Jie-Qiong Chen: Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University, School of Medicine, Shanghai 200080, China
Xiao-Huan Zhao: Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University, School of Medicine, Shanghai 200080, China
Yi-Min Wang: Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University, School of Medicine, Shanghai 200080, China
Yu-Hong Chen: Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University, School of Medicine, Shanghai 200080, China
Yu-Wei Wang: Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University, School of Medicine, Shanghai 200080, China
Xiao-Ling Wan: Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University, School of Medicine, Shanghai 200080, China; Shanghai Key Laboratory of Fundus Diseases, Shanghai 200080, China
Xue-Ting Luo: Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University, School of Medicine, Shanghai 200080, China; Shanghai Key Laboratory of Fundus Diseases, Shanghai 200080, China
Xiao-Dong Sun: Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University, School of Medicine, Shanghai 200080, China; Shanghai Key Laboratory of Fundus Diseases, Shanghai 200080, China; Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai 200080, China; National Clinical Research Center for Ophthalmic Diseases, Shanghai 200080, China

DOI: https://doi.org/10.18240/ijo.2021.09.07
Journal volume & issue: Vol. 14, no. 9
pp. 1334 – 1344

Abstract

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AIM: To illustrate the underlying mechanism how prominin-1 (also known as Prom1) mutation contribute to progressive photoreceptor degeneration. METHODS: A CRISPR-mediated Prom1 knockout (Prom1-KO) mice model in the C57BL/6 was generated and the photoreceptor degeneration phenotypes by means of structural and functional tests were demonstrated. Immunohistochemistry and immunoblot analysis were performed to reveal the localization and quantity of related outer segment (OS) proteins. RESULTS: The Prom1-KO mice developed the photoreceptor degeneration phenotype including the decreased outer nuclear layer (ONL) thickness and compromised electroretinogram amplitude. Immunohistochemistry analysis revealed impaired trafficking of photoreceptor OS proteins. Immunoblot data demonstrated decreased photoreceptor OS proteins. CONCLUSION: Prom1 deprivation causes progressive photoreceptor degeneration. Prom1 is essential for maintaining normal trafficking and normal quantity of photoreceptor OS proteins. The new light is shed on the pathogenic mechanism underlying photoreceptor degeneration caused by Prom1 mutation.

Published in International Journal of Ophthalmology

ISSN: 2222-3959 (Print); 2227-4898 (Online)
Publisher: Press of International Journal of Ophthalmology (IJO PRESS)
Country of publisher: China
LCC subjects: Medicine: Ophthalmology
Website: http://www.ijo.cn/gjyken/ch/index.aspx

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