RAPID COMMUNICATION Mice Lacking Granulocyte Colony-Stimulating Factor Have Chronic Neutropenia, Granulocyte and Macrophage Progenitor Cell Deficiency, and

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 lev-els were 20 % to 30 % of wild-type mice (genotype G-CSF+/ +) and mice heterozygousfor the null mutation had interme-diate 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. De-spite 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-I- mice had reduced numbers of neutrophils available for rapid mobiliza