PUBLICATION
Emc1 is essential for vision and zebrafish photoreceptor outer segment morphogenesis
- Authors
- McCann, T., Sundaramurthi, H., Walsh, C., Virdi, S., Alvarez, Y., Sapetto-Rebow, B., Collery, R.F., Carter, S.P., Moran, A., Mulholland, R., O'Connor, J.J., Taylor, M.R., Rauch, N., Starostik, M.R., English, M.A., Swaroop, A., Geisler, R., Reynolds, A.L., Kennedy, B.N.
- ID
- ZDB-PUB-241004-1
- Date
- 2024
- Source
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology 38: e70086e70086 (Journal)
- Registered Authors
- Alvarez, Yolanda, Collery, Ross, English, Milton A., Geisler, Robert, Kennedy, Breandan N., Reynolds, Alison, Taylor, Michael R., Virdi, Sanamjeet
- Keywords
- emc1, endoplasmic reticulum, inherited retinal disease, outer segment, photoreceptor, phototransduction, unfolded protein response, vasculature, zebrafish
- MeSH Terms
-
- Animals
- Membrane Proteins/genetics
- Membrane Proteins/metabolism
- Morphogenesis*
- Mutation
- Retina/metabolism
- Retinal Degeneration/genetics
- Retinal Degeneration/metabolism
- Retinal Degeneration/pathology
- Retinal Photoreceptor Cell Outer Segment/metabolism
- Vision, Ocular/genetics
- Vision, Ocular/physiology
- Zebrafish*
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 39360639 Full text @ FASEB J.
Citation
McCann, T., Sundaramurthi, H., Walsh, C., Virdi, S., Alvarez, Y., Sapetto-Rebow, B., Collery, R.F., Carter, S.P., Moran, A., Mulholland, R., O'Connor, J.J., Taylor, M.R., Rauch, N., Starostik, M.R., English, M.A., Swaroop, A., Geisler, R., Reynolds, A.L., Kennedy, B.N. (2024) Emc1 is essential for vision and zebrafish photoreceptor outer segment morphogenesis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 38:e70086e70086.
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 elucidate 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. These data shed light on why emc1 is a causative gene in inherited retinal disease and how outer segment morphogenesis is regulated.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping