Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Department of Ophthalmology, Johns Hopkins University, Baltimore, Maryland, USA.
Zebrafish. 2022 Jun;19(3):109-113. doi: 10.1089/zeb.2022.0020. Epub 2022 May 26.
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.
表达硝基还原酶（NTR）于特定细胞区室的斑马鱼系，使这些细胞对甲硝唑（MTZ）介导的消融敏感，已被证明对研究组织再生和研究细胞功能非常有用。与许多细胞不同，中性粒细胞对 NTR/MTZ 靶向消融策略相对具有抗性。最近，描述了 NTR 的一种合理设计的变体（NTR 2.0），其在斑马鱼中表现出大大改善的 MTZ 介导的消融功效。我们表明，具有中性粒细胞限制表达 NTR 2.0 的转基因系表现出完全的中性粒细胞消融，MTZ 剂量比当前的治疗方案少 100 倍，并且治疗持续时间短至 5 小时。
