Biswas, Lincoln

Han, Shanshan

Hu, Xuebin

Huang, Yuwen

Jiang, Tao

Li, Chang

Liu, Fei

Liu, Jing Yu

Liu, Mugen

Liu, Xiliang

Liu, Ying

Lu, Zhaojing

Reilly, James

Shu, Xinhua

Tang, Zhaohui

Wang, Lei

Wong, Fulton

Yu, Shanshan

Human Molecular Genetics

English

Shanshan Yu

Chang Li

Lincoln Biswas

Xuebin Hu

Fei Liu

James Reilly

Xiliang Liu

Ying Liu

Yuwen Huang

Zhaojing Lu

Shanshan Han

Lei Wang

Jing Yu Liu

Tao Jiang

Xinhua Shu

Fulton Wong

Zhaohui Tang

Mugen Liu

Crossref

CERKL gene knockout disturbs photoreceptor outer segment phagocytosis and causes rod-cone dystrophy in zebrafish

In humans, CERKL mutations cause widespread retinal degeneration: early dysfunction and loss of rod and cone photoreceptors in the outer retina and, progressively, death of cells in the inner retina. Despite intensive efforts, the function of CERKL remains obscure and studies in animal models have failed to clarify the disease mechanism of CERKL mutations. To address this gap in knowledge, we have generated a stable CERKL knockout zebrafish model by TALEN technology and a 7bp deletion in CERKL cDNA that caused the premature termination of CERKL. These CERKL-/- animals showed progressive degeneration of photoreceptor outer segments (OSs) and increased apoptosis of retinal cells, including those in the outer and inner retinal layers. Additionally, we confirmed by immunofluorescence and western-blot that rod degeneration in CERKL-/- zebrafish occurred earlier and was more significant than that in cone cells. Accumulation of shed OSs in the interphotoreceptor matrix was observed by transmission election microscopy (TEM). This suggested that CERKL may regulate the phagocytosis of OSs by the retinal pigment epithelium (RPE). We further found that the phagocytosis-associated protein MERTK was significantly reduced in CERKL-/- zebrafish. Additionally, in ARPE-19 cell lines, knockdown of CERKL also decreased the mRNA and protein level of MERTK, as well as the ox-POS phagocytosis. We conclude that CERKL deficiency in zebrafish may cause rod-cone dystrophy, but not cone-rod dystrophy, while interfering with the phagocytosis function of RPE associated with down-regulation of the expression of MERTK

ResearchOnline@GCU

https://researchonline.gcu.ac.uk/files/24952807/X.Shu_CERKL_HMG.pdf

CERKL gene knockout disturbs photoreceptor outer segment phagocytosis and causes rod-cone dystrophy in zebrafish

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ResearchOnline@GCU