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Emc1 is essential for vision and zebrafish photoreceptor outer segment morphogenesis

McCann, Tess; Sundaramurthi, Husvinee; Walsh, Ciara; Virdi, Sanamjeet 1; Alvarez, Yolanda; Sapetto-Rebow, Beata; Collery, Ross F.; Carter, Stephen P.; Moran, Ailis; Mulholland, Ruth; O'Connor, John J.; Taylor, Michael R.; Rauch, Nora; Starostik, Margaret R.; English, Milton A.; Swaroop, Anand; Geisler, Robert 1; Reynolds, Alison L.; Kennedy, Breandán N.
1 Karlsruher Institut für Technologie (KIT)

Abstract:

Inherited retinal diseases (IRDs) are a rare group of eye disorders characterized by progressive dysfunction and degeneration of retinal cells. In this study, we characterized the raifteirí (raf) zebrafish, a novel model of inherited blindness, identified through an unbiased ENU mutagenesis screen. A mutation in the largest subunit of the endoplasmic reticulum membrane protein complex, emc1 was subsequently identified as the causative raf mutation. We sought to eluci-date the cellular and molecular phenotypes in the emc1−/− knockout model and explore the association of emc1 with retinal degeneration. Visual behavior and retinal electrophysiology assays demonstrated that emc1−/− mutants had severe visual impairments. Retinal histology and morphometric analysis revealed extensive abnormalities, including thinning of the photoreceptor layer, in addition to large gaps surrounding the lens. Notably, photoreceptor outer segments were drastically smaller, outer segment protein expression was altered and hyaloid vasculature development was disrupted. Transcriptomic profiling identified cone and rod-specific phototransduction genes significantly downregulated by loss of emc1. ... mehr


Verlagsausgabe §
DOI: 10.5445/IR/1000175305
Veröffentlicht am 18.10.2024
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Toxikologie und Genetik (ITG)
Publikationstyp Zeitschriftenaufsatz
Publikationsdatum 15.10.2024
Sprache Englisch
Identifikator ISSN: 0892-6638, 1530-6860
KITopen-ID: 1000175305
Erschienen in The FASEB Journal
Verlag Federation of American Society of Experimental Biology (FASEB)
Band 38
Heft 19
Seiten Art.-Nr.: e70086
Vorab online veröffentlicht am 03.10.2024
Nachgewiesen in Scopus
Web of Science
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