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Zebrafish G-CSFR maintains neutrophil number and function throughout the lifespan.

Infection and Immunity 2018 November 20
Granulocyte colony-stimulating factor receptor (G-CSFR), encoded by the CSF3R 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 csf3r 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. This study has identified an important role for the zebrafish G-CSFR in maintaining the number and functionality of neutrophils throughout the lifespan and created a bone fide zebrafish model of non-responsive neutropenia.

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