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The effects of ush2a gene knockout on vesicle transport in photoreceptors.

Authors :
Han S
Wang Q
Cheng M
Hu Y
Liu P
Hou W
Liang L
Source :
Gene [Gene] 2024 Jan 20; Vol. 892, pp. 147885. Date of Electronic Publication: 2023 Oct 07.
Publication Year :
2024

Abstract

USH2A (Usher syndrome type 2A) gene mutations are the predominant cause of Usher syndrome type 2, characterized by sensorineural hearing loss and retinitis pigmentosa (RP), and also significant contributors to non-syndromic RP. To date, there is a lack of definitive therapeutic interventions to mitigate the associated disorders caused by USH2A mutations, and the precise pathogenic mechanisms underlying their onset remain unclear. In the present study, we utilized the ush2a knockout zebrafish model to investigate the pathological mechanisms of RP. In late-stage ush2a <superscript>-/-</superscript> zebrafish, the outer segments of rods displayed shortened length and decreased number. Anomalous vesicle accumulation was observed at the junction between the inner and outer segments, accompanied by reduced expression and structural damage of actin filaments in the photoreceptor cells. Furthermore, we discovered that Rab8 expression was downregulated and exhibited aberrant localization in ush2a <superscript>-/-</superscript> zebrafish. Additionally, we identified an interaction between USH2A and Rab8. Therefore, the knockout of ush2a may potentially affect vesicle transport through the regulation of Rab8, providing a novel target for maintaining the survival of photoreceptor cells. These findings also contribute to our understanding of the potential molecular pathogenesis underlying RP caused by USH2A gene mutations.<br />Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2023. Published by Elsevier B.V.)

Details

Language :
English
ISSN :
1879-0038
Volume :
892
Database :
MEDLINE
Journal :
Gene
Publication Type :
Academic Journal
Accession number :
37813209
Full Text :
https://doi.org/10.1016/j.gene.2023.147885