一种用于快速完全中性粒细胞清除的新型转基因系。
A New Transgenic Line for Rapid and Complete Neutrophil Ablation.
机构信息
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.
出版信息
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。
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