A role for G-CSF receptor signaling in the regulation of hematopoietic cell function but not lineage commitment or differentiation.
To investigate the specificity of cytokine signals in hematopoietic differentiation, we generated mice with a targeted mutation of their G-CSF receptor (G-CSFR) such that the cytoplasmic (signaling) domain of the G-CSFR is replaced with the cytoplasmic domain of the erythropoietin receptor. In homozygous mutant mice, expression of this chimeric receptor had no apparent affect on lineage commitment and was able to support the production of morphologically mature neutrophils. However, mutant neutrophils displayed reduced chemotaxis, and G-CSF-stimulated mobilization of neutrophils and hematopoietic progenitors from the bone marrow to blood was markedly impaired. Thus, the G-CSFR is generating unique signals that are required for certain specialized hematopoietic cell functions but are not required for granulocytic differentiation or lineage commitment.
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Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110-1093, USA.
Poursine-Laurent
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Liu
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D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D016209:Interleukin-8 / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D017467:Receptors, Erythropoietin / Q000502:physiology; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000502:physiology*
D016209:Interleukin-8; D017467:Receptors, Erythropoietin; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor