Chemical screening reveals Ronidazole is a superior prodrug to Metronidazole for nitroreductase-induced cell ablation system in zebrafish larvae  

作　　者：Siting Lai Ankita Kumari Jixiang Liu Yiyue Zhang Wenqing Zhang Kuangyu Yen Jin Xu 

机构地区：[1]Department of Developmental Biology,School of Basic Medical Sciences,Southern Medical University,Guangzhou 510515,China [2]Division of Cell,Developmental and Integrative Biology,School of Medicine,South China University of Technology,Guangzhou 510006,China

出　　处：《Journal of Genetics and Genomics》2021年第12期1081-1090,共10页遗传学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(31771594,31970763);National Natural Science Foundation of China(NSFC)/Research Grants Council(RGC)Joint Research Scheme(31961160726);Guangdong Science and Technology Plan projects(2019A030317001)。

摘　　要：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. Our results,taken together, indicate that Ronidazole is a superior prodrug to MTZ for the NTR system, especially for the study of neuron regeneration in zebrafish larvae.

关 键 词：MTZ Ronidazole NTR Cell ablation Regeneration ZEBRAFISH 

分 类 号：Q2-33[生物学—细胞生物学]