PUBLICATION
Elovl4b Knockout Zebrafish as a Model for Ocular Very-Long-Chain Polyunsaturated Fatty Acid Deficiency
- Authors
- Nwagbo, U., Parvez, S., Maschek, J.A., Bernstein, P.S.
- ID
- ZDB-PUB-240212-4
- Date
- 2024
- Source
- Journal of Lipid Research 65(3): 100518 (Journal)
- Registered Authors
- Bernstein, Paul S., Nwagbo, Uzoamaka
- Keywords
- ELOVL4, lipids, retinal degeneration, very long-chain polyunsaturated fatty acids, zebrafish
- MeSH Terms
-
- Chromatography, Liquid
- Mice
- Animals
- Fatty Acids, Unsaturated
- Tandem Mass Spectrometry*
- Retina
- Eye Proteins/genetics
- Zebrafish*/genetics
- PubMed
- 38342437 Full text @ J. Lipid Res.
Citation
Nwagbo, U., Parvez, S., Maschek, J.A., Bernstein, P.S. (2024) Elovl4b Knockout Zebrafish as a Model for Ocular Very-Long-Chain Polyunsaturated Fatty Acid Deficiency. Journal of Lipid Research. 65(3):100518.
Abstract
Very-long-chain polyunsaturated fatty acids (VLC-PUFAs) are a group of lipids with chain lengths >24 carbons, and the ELOVL4 enzyme is responsible for the rate-limiting step in vertebrate VLC-PUFA biosynthesis. Studies on the role of VLC-PUFAs in vision have been hindered due to the need for adequate animal models to capture the global loss of VLC-PUFAs. Since homozygous Elovl4 ablation is lethal in neonatal mice due to catastrophic drying from the loss of their protective skin barrier, we established a zebrafish model of Elovl4 ablation. We generated Elovl4b knockout zebrafish by creating a 56-bp deletion mutation in exon 2 of the Elovl4b gene using CRISPR-Cas9. We used GC-MS and LC-MS/MS to analyze the VLC-PUFA and lipid profiles from adult wild-type and Elovl4b knockout fish eyes. We also performed histology and visual-behavioral tests. We found that heterozygous and homozygous Elovl4b knockout zebrafish eyes had altered lipid profiles and a significantly lower C30 to C36 VLC-PUFA abundance than age-matched wild-type fish. Moreover, Elovl4b+/- and Elovl4b-/- knockout larvae had significantly lower motor activity in response to light-dark cycles in the visual-motor response test than their age-matched controls. Elovl4b-/- adult fish showed no obvious differences in gross retinal morphology and lamination compared to wild-type, except for the presence of lipid droplets within the retinal pigment epithelial cell layer of Elovl4b-/- fish. Our data indicate that the loss of Elovl4b in zebrafish can cause changes in lipid profiles, visual abnormalities, and subtle retinal changes. These findings highlight the use of zebrafish as a model for VLC-PUFA-depletion and ELOVL4-related dysfunction.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping