MICE LACKING GRANULOCYTE-COLONY-STIMULATING FACTOR HAVE CHRONIC NEUTROPENIA, GRANULOCYTE AND MACROPHAGE PROGENITOR-CELL DEFICIENCY, AND IMPAIRED NEUTROPHIL MOBILIZATION
Details
Publication Year 1994-09-15, Volume 84, Issue #6, Page 1737-1746
Journal Title
BLOOD
Publication Type
Journal Article
Abstract
Mice lacking granulocyte colony-stimulating factor (G-CSF) were generated by targeted disruption of the G-CSF gene in embryonal stem cells. G-CSF-deficient mice (genotype G-CSF-/-) are viable, fertile, and superficially healthy, but have a chronic neutropenia. Peripheral blood neutrophil levels were 20% to 30% of wild-type mice (genotype G-CSF+/+) and mice heterozygous for the null mutation had intermediate neutrophil levels, suggesting a gene-dosage effect. In the marrow of G-CSF-/- mice, granulopoietic precursor cells were reduced by 50% and there were reduced levels of granulocyte, macrophage, and blast progenitor cells. Despite G-CSF deficiency, mature neutrophils were still present in the blood and marrow, indicating that other factors can support neutrophil production in vivo. G-CSF-/- mice had reduced numbers of neutrophils available for rapid mobilization into the circulation by a single dose of G-CSF. G-CSF administration reversed the granulopoietic defect of G-CSF-/- mice. One day of G-CSF administration to G-CSF-/- mice elevated circulating neutrophil levels to normal, and after 4 days of G-CSF administration, G-CSF+/+ and G-CSF-/- marrows were morphologically indistinguishable. G-CSF-/- mice had a markedly impaired ability to control infection with Listeria monocytogenes, with diminished neutrophil and delayed monocyte increases in the blood and reduced infection-driven granulopoiesis. Collectively, these observations indicate that G-CSF is indispensible for maintaining the normal quantitative balance of neutrophil production during ''steady-state'' granulopoiesis in vivo and also implicate G-CSF in ''emergency'' granulopoiesis during infections. (C) 1994 by The American Society of Hematology.
Publisher
W B SAUNDERS CO
Keywords
INVIVO; GENE; MOUSE; CSF; GRANULOPOIESIS; INFECTION; MUTATION
Rights Notice
Refer to copyright notice on published article.


Creation Date: 1994-09-15 12:00:00
Last Modified: 0001-01-01 12:00:00
An error has occurred. This application may no longer respond until reloaded. Reload 🗙