Elovl4b knockout zebrafish as a model for ocular very-long-chain PUFA deficiency
Bibliographic record
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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".