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
  • Zebrafish Proteins*/genetics
  • Zebrafish Proteins*/metabolism
  • Mutation
  • Retina/metabolism
  • Vision, Ocular/genetics
  • Vision, Ocular/physiology
  • Zebrafish*
  • Morphogenesis*
  • Membrane Proteins/genetics
  • Membrane Proteins/metabolism
  • Retinal Photoreceptor Cell Outer Segment/metabolism
  • Retinal Degeneration/genetics
  • Retinal Degeneration/metabolism
  • Retinal Degeneration/pathology
(all 15)
PubMed
39360639 Full text @ FASEB J.
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
Figures
Figure Gallery (8 images)
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Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ucd10TgTransgenic Insertion
    ucd15
      		Unknown
      y1TgTransgenic Insertion
        1 - 3 of 3
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        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        No data available
        Fish
        No data available
        Antibodies
        Orthology
        No data available
        Engineered Foreign Genes
        Marker Marker Type Name
        EGFPEFGEGFP
        1 - 1 of 1
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        Mapping
        No data available
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        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.