School of Medicine, Deakin University, Geelong, VIC, Australia.
Institute for Mental and Physical Health and Clinical Translation (IMPACT), Deakin University, Geelong, VIC, Australia.
Front Immunol. 2023 Jan 10;13:1095453. doi: 10.3389/fimmu.2022.1095453. eCollection 2022.
The granulocyte colony-stimulating factor receptor (G-CSFR), encoded by the gene, is involved in the production and function of neutrophilic granulocytes. Somatic mutations in leading to truncated G-CSFR forms are observed in acute myeloid leukemia (AML), particularly those subsequent to severe chronic neutropenia (SCN), as well as in a subset of patients with other leukemias.
This investigation introduced equivalent mutations into the zebrafish gene genome editing and used a range of molecular and cellular techniques to understand the impact of these mutations on immune cells across the lifespan.
Zebrafish harboring truncated G-CSFRs showed significantly enhanced neutrophil production throughout successive waves of embryonic hematopoiesis and a neutrophil maturation defect in adults, with the mutations acting in a partially dominant manner.
This study has elucidated new insights into the impact of G-CSFR truncations throughout the life-course and created a zebrafish model for further investigation.
粒细胞集落刺激因子受体（G-CSFR）由 基因编码，参与中性粒细胞的生成和功能。导致截短 G-CSFR 形式的 基因突变在急性髓细胞白血病（AML）中观察到，特别是在严重慢性中性粒细胞减少症（SCN）之后，以及在一部分其他白血病患者中观察到。
本研究通过基因组编辑将等效突变引入斑马鱼 基因，并使用一系列分子和细胞技术来了解这些突变对整个生命周期内免疫细胞的影响。
携带截短 G-CSFR 的斑马鱼在连续的胚胎造血过程中表现出明显增强的中性粒细胞生成，并且在成年时存在中性粒细胞成熟缺陷，这些突变以部分显性方式发挥作用。
本研究阐明了 G-CSFR 截断对整个生命过程的影响的新见解，并创建了一个用于进一步研究的 斑马鱼模型。
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