biostudies-literatureUnknown13Bulleeraz V<h4>Introduction</h4>The granulocyte colony-stimulating factor receptor (G-CSFR), encoded by the <i>CSF3R</i> gene, is involved in the production and function of neutrophilic granulocytes. Somatic mutations in <i>CSF3R</i> 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.<h4>Methods</h4>This investigation introduced equivalent mutations into the zebrafish <i>csf3r</i> gene <i>via</i> genome editing and used a range of molecular and cellular techniques to understand the impact of these mutations on immune cells across the lifespan.<h4>Results</h4>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.<h4>Discussion</h4>This study has elucidated new insights into the impact of G-CSFR truncations throughout the life-course and created a <i>bone fide</i> zebrafish model for further investigation.Frontiers in immunology1095453https://www.ebi.ac.uk/biostudies/studies/S-EPMC9871641biostudies-literatureLeukemia-associated truncation of granulocyte colony-stimulating factor receptor impacts granulopoiesis throughout the life-course.PMC9871641Goy MBulleeraz VLiongue CBasheer FWard ACfalseLeukemia-associated truncation of granulocyte colony-stimulating factor receptor impacts granulopoiesis throughout the life-course.<h4>Introduction</h4>The granulocyte colony-stimulating factor receptor (G-CSFR), encoded by the <i>CSF3R</i> gene, is involved in the production and function of neutrophilic granulocytes. Somatic mutations in <i>CSF3R</i> 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.<h4>Methods</h4>This investigation introduced equivalent mutations into the zebrafish <i>csf3r</i> gene <i>via</i> genome editing and used a range of molecular and cellular techniques to understand the impact of these mutations on immune cells across the lifespan.<h4>Results</h4>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.<h4>Discussion</h4>This study has elucidated new insights into the impact of G-CSFR truncations throughout the life-course and created a <i>bone fide</i> zebrafish model for further investigation.2022-01-01T00:00:00Z20222025-04-22T06:15:40.311Z2025-04-05T21:40:07.295ZS-EPMC98716413670397410.3389/fimmu.2022.1095453