School of Medicine, Deakin University, Geelong, Victoria, Australia.
Centre for Molecular and Medical Research, Deakin University, Geelong, Victoria, Australia.
Infect Immun. 2019 Jan 24;87(2). doi: 10.1128/IAI.00793-18. Print 2019 Feb.
Granulocyte colony-stimulating factor receptor (G-CSFR), encoded by the gene, represents a major regulator of neutrophil production and function in mammals, with inactivating extracellular mutations identified in a cohort of neutropenia patients unresponsive to G-CSF treatment. This study sought to elucidate the role of the zebrafish G-CSFR by generating mutants harboring these inactivating extracellular mutations using genome editing. Zebrafish mutants possessed significantly decreased numbers of neutrophils from embryonic to adult stages, which were also functionally compromised, did not respond to G-CSF, and displayed enhanced susceptibility to bacterial infection. The study has identified an important role for the zebrafish G-CSFR in maintaining the number and functionality of neutrophils throughout the life span and created a zebrafish model of nonresponsive neutropenia.
粒细胞集落刺激因子受体 (G-CSFR) 由 基因编码，是哺乳动物中性粒细胞生成和功能的主要调节因子，在一组对 G-CSF 治疗无反应的中性粒细胞减少症患者中发现了失活的细胞外突变。本研究旨在通过使用基因组编辑生成携带这些失活细胞外突变的突变体来阐明斑马鱼 G-CSFR 的作用。斑马鱼 突变体在胚胎到成年阶段的中性粒细胞数量显著减少，其功能也受到损害，对 G-CSF 无反应，并且对细菌感染的敏感性增强。该研究确定了斑马鱼 G-CSFR 在整个生命周期维持中性粒细胞数量和功能中的重要作用，并创建了一种对中性粒细胞减少症无反应的斑马鱼模型。
