Zebrafish Granulocyte Colony-Stimulating Factor Receptor Maintains Neutrophil Number and Function throughout the Life Span.

Abstract

Granulocyte colony-stimulating factor receptor (G-CSFR), encoded by thegene, 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. Zebrafishmutants 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 azebrafish model of nonresponsive neutropenia.