Modelling Peroxisomal Disorders in Zebrafish
Abstract
1. Introduction
2. Visualisation of Peroxisomes in Zebrafish
3. Peroxisomal Protein Inventory and Metabolic Pathways in Zebrafish
4. Zebrafish Models of Peroxisomal Disorders
4.1. Peroxisome Biogenesis Disorders/Zellweger Spectrum Disorders
4.1.1. pex2 Mutant Zebrafish
Human Disorder | Targeted Gene | Method | Studied Tissues | Peroxisomal Phenotypes | Phenotypes Related to Clinical Features | Ref. |
---|---|---|---|---|---|---|
ZSD | pex2 | TALENs- mediated knockout | Liver Brain Eyes Muscles | ↓ Peroxisomal matrix protein import ↓ Catalase and glutathione peroxidase activities ↑ VLCFAs ↓ Ether phospholipids | △ Motor activity Hypotonia ↑ Hepatic lipid △ Neuronal and muscle function △ Gametogenesis ↓ Crystallin genes ↓ Survival | [63] |
ZSD | pex5 | CRISPR/Cas9-mediated knockout | Liver Nervous system Whole larvae | ↓ Peroxisomal matrix protein import ↓ Peroxisome abundance | △ Motor activity Demyelination ↑ Hepatic lipid Edema Deflated swim bladder Shrunken liver ↓ Survival Expedited death under fasting conditions | [69] |
ZSD | pex13 | CRISPR/Cas9-mediated knockout | Liver Whole larvae | ↓ Peroxisomal matrix protein import ↓ Peroxisome abundance ↑ Ubiquitinated PEX5 ↑ Peroxisome-dependent ROS ↑ Pexophagy | △ Motor activity ↑ Hepatic lipid accumulation △ Neuronal function Liver steatosis Laval mortality | [38] |
pex13 | Morpholino- mediated knockout (mosaic) | Liver Pronephric duct Yolk sac | Partial elimination of peroxisomes | Not assessed | [30] | |
ALD | abcd1 | TALENs- mediated knockout | CNS Adrenal glands Whole embryo | ↑ VLCFAs ↑ Cholesterol | △ Motor activity Hypomyelination △ Oligodendrocyte patterning △ CNS development ↑ Apoptosis ↓ Survival | [70] |
Mitchell Syndrome | acox1 | Transient overexpression (N237S) | Brain Spinal cord Whole embryo | ↓ Peroxisome density ↑ Oxidative stress | △ Motor activity Activation of ISR ↓ Survival | [71] |
D-BPD | dbp | Morpholino- mediated knockdown | Whole embryo Liver Pancreas | ↓ beta-oxidation ↓ Ether phospholipids synthesis ↓ pex5 expression | △ Yolk lipid consumption Growth retardation Morphological malformation △ Neuronal, liver, pancreas, cartilage, blood, blood vessels, digestive organ development Abnormal vascular patterning Embryonic lethality | [55] |
Osteoarthritis | fis1 | Morpholino- mediated knockdown | Whole embryo | ↓ Peroxisome abundance ↓ Catalase and glutathione peroxidase activities ↓ beta-oxidation gene expression | ↑ Apoptosis ↑ Lipid ↓ Survival | [37] |
Unspecified | vwa8 | Morpholino- mediated knockdown | Whole embryo | Not assessed | △ Motor activity Developmental delays and defects Light sensitivity Facial dysmorphism ↓ Survival | [72] |
Autosomal-dominant retinitis pigmentosa | vwa8 | Morpholino- mediated knockdown | Retina Photoreceptor layer | Not assessed | △ Visual function Retinal pigment deposition Thinning of the retinal photoreceptor layer | [73] |
4.1.2. pex3 Mutant Zebrafish
4.1.3. pex5 Mutant Zebrafish
4.1.4. pex13 Mutant Zebrafish
4.2. Peroxisomal Single Enzyme Deficiency
Adrenoleukodystrophy (ALD) Model Zebrafish
4.3. Peroxisomal Beta-Oxidation Deficiency
4.3.1. ACOX1 Mutant Disease Model Zebrafish
4.3.2. D-Bifunctional Protein (Dbp) Deficiency Model Zebrafish
4.4. Dually Targeted Peroxisomal/Mitochondrial Protein Deficiency
4.4.1. Fission 1 (FIS1) Deficiency Model Zebrafish
4.4.2. VWA8 Deficiency Model Zebrafish
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Function/Pathway | Comments | Dr | Hs |
---|---|---|---|
Fatty acid beta-oxidation | Acox2 is absent in zebrafish ACOXL/ACOX4 is present in humans and zebrafish, but not well defined | ||
Bile acid synthesis | Bile acid-CoA:amino acid N-acyltransferase (Baat) is absent in zebrafish | - | |
Fatty acid alpha-oxidation | |||
Saturation of PUFAs | |||
Ether lipid synthesis | |||
Glycolate/ Glyoxylate metabolism | Hydroxyacid oxidase 3 (Hao3) is absent in zebrafish | ||
Amino acid catabolism | D-amino acid oxidases 2 and 3 (Dao2, Dao3) are absent in humans | ||
Amine metabolism | |||
Purine and pyrimidine metabolism | Urate oxidase (Uricase) (Uox), Allantoicase (Allc), Urate (5-hydroxyiso-) hydrolase a (Uraha), Ureidoimidazoline decarboxylase (Urad) are absent or inactivated in humans | - | |
Oxygen metabolism/ Oxidation redox equivalents | |||
Proteases | |||
Carbohydrate metabolism |
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Jiang, C.S.; Schrader, M. Modelling Peroxisomal Disorders in Zebrafish. Cells 2025, 14, 147. https://doi.org/10.3390/cells14020147
Jiang CS, Schrader M. Modelling Peroxisomal Disorders in Zebrafish. Cells. 2025; 14(2):147. https://doi.org/10.3390/cells14020147
Chicago/Turabian StyleJiang, Chenxing S., and Michael Schrader. 2025. "Modelling Peroxisomal Disorders in Zebrafish" Cells 14, no. 2: 147. https://doi.org/10.3390/cells14020147
APA StyleJiang, C. S., & Schrader, M. (2025). Modelling Peroxisomal Disorders in Zebrafish. Cells, 14(2), 147. https://doi.org/10.3390/cells14020147