PUBLICATION
The Abcc6a Knockout Zebrafish Model as a Novel Tool for Drug Screening for Pseudoxanthoma Elasticum
- Authors
- Van Gils, M., Willaert, A., Coucke, P.J., Vanakker, O.M.
- ID
- ZDB-PUB-220324-3
- Date
- 2022
- Source
- Frontiers in pharmacology 13: 822143 (Journal)
- Registered Authors
- Coucke, Paul, Willaert, Andy
- Keywords
- alendronate, compound screening, etidronate, magnesium citrate, pseudoxanthoma elasticum, sodium thiosulfate, vitamin K1, zebrafish
- MeSH Terms
- none
- PubMed
- 35317004 Full text @ Front Pharmacol
Citation
Van Gils, M., Willaert, A., Coucke, P.J., Vanakker, O.M. (2022) The Abcc6a Knockout Zebrafish Model as a Novel Tool for Drug Screening for Pseudoxanthoma Elasticum. Frontiers in pharmacology. 13:822143.
Abstract
Pseudoxanthoma elasticum (PXE) is a multisystem ectopic mineralization disorder caused by pathogenic variants in the ABCC6 gene. Though complications of the disease can be treated, PXE itself remains currently intractable. A strategy for rapid and cost-effective discovery of therapeutic drugs would be to perform chemical compound screening using zebrafish, but this approach remains to be validated for PXE. In this paper, we validate a stable CRISPR/Cas9 abcc6a knockout zebrafish model-which has spinal column hypermineralization as its primary phenotypic feature-as a model system for compound screening in ectopic mineralization. We evaluated the anti-mineralization potential of five compounds, which had (anecdotal) positive effects reported in Abcc6 knockout mice and/or PXE patients. Abcc6a knockout zebrafish larvae were treated from 3 to 10 days post-fertilization with vitamin K1, sodium thiosulfate, etidronate, alendronate or magnesium citrate and compared to matching controls. Following alizarin red S staining, alterations in notochord sheath mineralization were semiquantified and found to largely congrue with the originally reported outcomes. Our results demonstrate that the use of this abcc6a knockout zebrafish model is a validated and promising strategy for drug discovery against ectopic mineralization.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping