PUBLICATION
Chemical screening reveals Ronidazole is a superior pro-drug to Metronidazole for Nitroreductase-induced cell ablation system in zebrafish larvae
- Authors
- Lai, S., Kumari, A., Liu, J., Zhang, Y., Zhang, W., Yen, K., Xu, J.
- ID
- ZDB-PUB-210820-10
- Date
- 2021
- Source
- Journal of genetics and genomics = Yi chuan xue bao 48(12): 1081-1090 (Journal)
- Registered Authors
- Kumari, Ankita, Xu, Jin, Zhang, Wenqing, Zhang, Yiyue
- Keywords
- Cell ablation, MTZ, NTR, Regeneration, Ronidazole, Zebrafish
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Larva/metabolism
- Metronidazole/metabolism
- Metronidazole/pharmacology
- Nitroreductases/genetics
- Nitroreductases/metabolism
- Prodrugs*/metabolism
- Prodrugs*/pharmacology
- Ronidazole
- Zebrafish*/metabolism
- PubMed
- 34411714 Full text @ J. Genet. Genomics
Citation
Lai, S., Kumari, A., Liu, J., Zhang, Y., Zhang, W., Yen, K., Xu, J. (2021) Chemical screening reveals Ronidazole is a superior pro-drug to Metronidazole for Nitroreductase-induced cell ablation system in zebrafish larvae. Journal of genetics and genomics = Yi chuan xue bao. 48(12):1081-1090.
Abstract
The Metronidazole (MTZ)/nitroreductase (NTR)-mediated cell ablation system is the most commonly used chemical-genetic cell ablation method in zebrafish. This system can specifically ablate target cells under spatial and temporal control. The MTZ/NTR system has become a widely used cell ablation system in biological, developmental, and functional studies. However, the inadequate cell-ablation ability of some cell types and the side effects of high concentration MTZ impede extensive applications of the MTZ/NTR system. In the present study, the US drug collection library was searched to extend the NTR system. Six MTZ analogs were found and the cell-ablation ability of these analogs was tested in zebrafish larvae. The results revealed that two of the NTR substrates, Furazolidone and Ronidazole, ablated target cells more efficiently than MTZ at lower concentrations. Furthermore, the working concentration of Ronidazole, but not Furazolidone and MTZ, did not affect axonal bridge formation during spinal cord regeneration. Taken together, our results indicate that Ronidazole is a superior pro-drug to MTZ for the NTR system, especially for the study of neuron regeneration in zebrafish larvae.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping