期刊
ZEBRAFISH
卷 19, 期 3, 页码 109-113出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/zeb.2022.0020
关键词
neutrophil; ablation; nitroreductase; NTR 2; 0; metronidazole
资金
- Health Research Council of New Zealand [19/750, 21/310]
- National Institutes of Health of the United States [R01OD020376]
This article investigates a new approach to target neutrophils using an improved variant of NTR, showing that it is more effective than current treatment regimens.
Zebrafish lines expressing nitroreductase (NTR) in specific cell compartments, which sensitizes those cells to metronidazole (MTZ)-mediated ablation, have proven extremely useful for studying tissue regeneration and investigating cell function. In contrast to many cells, neutrophils are comparatively resistant to the NTR/MTZ targeted ablation strategy. Recently, a rationally engineered variant of NTR (NTR 2.0) has been described that exhibits greatly improved MTZ-mediated ablation efficacy in zebrafish. We show that a transgenic line with neutrophil-restricted expression of NTR 2.0 demonstrates complete neutrophil ablation, with an MTZ dose 100-fold less than current treatment regimens, and with treatment durations as short as 5 h.
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