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Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Mice lacking granulocyte colony-stimulating factor have chronic neutropenia, granulocyte and macrophage progenitor cell deficiency, and impaired neutrophil mobilization GJ Lieschke, D Grail, G Hodgson, D Metcalf, E Stanley, C Cheers, KJ Fowler, S Basu, YF Zhan and AR Dunn Melbourne Tumor Biology Branch, Ludwig Institute for Cancer Research, Parkville, Victoria, Australia. 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. Volume 84, Issue 6, pp. 1737-1746, 09/15/1994 Copyright © 1994 by The American Society of Hematology CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Kimura, M. A. Rieger, J. M. Simone, W. Chen, M. C. Wickre, B.-M. Zhu, P. S. Hoppe, J. J. O'Shea, T. Schroeder, and L. Hennighausen The transcription factors STAT5A/B regulate GM-CSF-mediated granulopoiesis Blood, November 19, 2009; 114(21): 4721 - 4728. [Abstract] [Full Text] [PDF] K. Diederich, S. Sevimli, H. Dorr, E. Kosters, M. Hoppen, L. Lewejohann, R. Klocke, J. Minnerup, S. Knecht, S. Nikol, et al. 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Yeaman Mice Lacking the Chemokine Receptor CCR1 Show Increased Susceptibility to Toxoplasma gondii Infection J. Immunol., February 1, 2001; 166(3): 1930 - 1937. [Abstract] [Full Text] [PDF] B. D. Car and V. M. Eng Special Considerations in the Evaluation of the Hematology and Hemostasis of Mutant Mice Vet. Pathol., January 1, 2001; 38(1): 20 - 30. [Abstract] [Full Text] [PDF] K. Nakamura, M. Kobayashi, N. Konishi, H. Kawaguchi, S.-i. Miyagawa, T. Sato, H. Toyoda, Y. Komada, S. Kojima, O. Katoh, et al. Abnormalities of primitive myeloid progenitor cells expressing granulocyte colony-stimulating factor receptor in patients with severe congenital neutropenia Blood, December 15, 2000; 96(13): 4366 - 4369. [Abstract] [Full Text] [PDF] S. Basu, G. Hodgson, H.-H. Zhang, M. Katz, C. Quilici, and A. R. Dunn "Emergency" granulopoiesis in G-CSF-deficient mice in response to Candida albicans infection Blood, June 15, 2000; 95(12): 3725 - 3733. [Abstract] [Full Text] [PDF] P. Schwarzenberger, W. Huang, P. Ye, P. Oliver, M. Manuel, Z. Zhang, G. Bagby, S. Nelson, and J. K. Kolls Requirement of Endogenous Stem Cell Factor and Granulocyte-Colony-Stimulating Factor for IL-17-Mediated Granulopoiesis J. Immunol., May 1, 2000; 164(9): 4783 - 4789. [Abstract] [Full Text] [PDF] P. G. Lutz, C. Moog-Lutz, E. Coumau-Gatbois, L. Kobari, Y. Di Gioia, and Y. E. Cayre Myeloblastin is a granulocyte colony-stimulating factor-responsive gene conferring factor-independent growth to hematopoietic cells PNAS, February 15, 2000; 97(4): 1601 - 1606. [Abstract] [Full Text] [PDF] S.-M. Luoh, E. Stefanich, G. Solar, H. Steinmetz, T. Lipari, T. I. Pestina, C. W. Jackson, and F. J. de Sauvage Role of the Distal Half of the c-Mpl Intracellular Domain in Control of Platelet Production by Thrombopoietin In Vivo Mol. Cell. Biol., January 15, 2000; 20(2): 507 - 515. [Abstract] [Full Text] N. Konishi, M. Kobayashi, S.-i. Miyagawa, T. Sato, O. Katoh, and K. Ueda Defective Proliferation of Primitive Myeloid Progenitor Cells in Patients With Severe Congenital Neutropenia Blood, December 15, 1999; 94(12): 4077 - 4083. [Abstract] [Full Text] [PDF] M. Y. Chiang and J. G. Monroe BSAP/Pax5A Expression Blocks Survival and Expansion of Early Myeloid Cells Implicating Its Involvement in Maintaining Commitment to the B-Lymphocyte Lineage Blood, December 1, 1999; 94(11): 3621 - 3632. [Abstract] [Full Text] [PDF] E. T. Harvill, P. A. Cotter, and J. F. Miller Pregenomic Comparative Analysis between Bordetella bronchiseptica RB50 and Bordetella pertussis Tohama I in Murine Models of Respiratory Tract Infection Infect. Immun., November 1, 1999; 67(11): 6109 - 6118. [Abstract] [Full Text] [PDF] K. L. Anderson, K. A. Smith, H. Perkin, G. Hermanson, C.-G. Anderson, D. J. Jolly, R. A. Maki, and B. E. Torbett PU.1 and the Granulocyte- and Macrophage Colony-Stimulating Factor Receptors Play Distinct Roles in Late-Stage Myeloid Cell Differentiation Blood, October 1, 1999; 94(7): 2310 - 2318. [Abstract] [Full Text] [PDF] T. Kanayasu-Toyoda, T. Yamaguchi, E. Uchida, and T. Hayakawa Commitment of Neutrophilic Differentiation and Proliferation of HL-60 Cells Coincides with Expression of Transferrin Receptor. EFFECT OF GRANULOCYTE COLONY STIMULATING FACTOR ON DIFFERENTIATION AND PROLIFERATION J. Biol. Chem., September 3, 1999; 274(36): 25471 - 25480. [Abstract] [Full Text] [PDF] A. C. Ward, Y. M. van Aesch, J. Gits, A. M. Schelen, J. P. de Koning, D. van Leeuwen, M. H. Freedman, and I. P. Touw Novel Point Mutation in the Extracellular Domain of the Granulocyte Colony-Stimulating Factor (G-Csf) Receptor in a Case of Severe Congenital Neutropenia Hyporesponsive to G-Csf Treatment J. Exp. Med., August 16, 1999; 190(4): 497 - 508. [Abstract] [Full Text] [PDF] X. Wang, E. Scott, C. L. Sawyers, and A. D. Friedman C/EBPalpha Bypasses Granulocyte Colony-Stimulating Factor Signals to Rapidly Induce PU.1 Gene Expression, Stimulate Granulocytic Differentiation, and Limit Proliferation in 32D cl3 Myeloblasts Blood, July 15, 1999; 94(2): 560 - 571. [Abstract] [Full Text] [PDF] J.-L. Vincent Prevention of nosocomial bacterial pneumonia Thorax, June 1, 1999; 54(6): 544 - 549. [Full Text] T. Yamaguchi, T. Mukasa, E. Uchida, T. Kanayasu-Toyoda, and T. Hayakawa The Role of STAT3 in Granulocyte Colony-stimulating Factor-induced Enhancement of Neutrophilic Differentiation of Me2SO-treated HL-60 Cells. GM-CSF INHIBITS THE NUCLEAR TRANSLOCATION OF TYROSINE-PHOSPHORYLATED STAT3 J. Biol. Chem., May 28, 1999; 274(22): 15575 - 15581. [Abstract] [Full Text] [PDF] A. C. Ward, L. Smith, J. P. de Koning, Y. van Aesch, and I. P. Touw Multiple Signals Mediate Proliferation, Differentiation, and Survival from the Granulocyte Colony-stimulating Factor Receptor in Myeloid 32D Cells J. Biol. 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Touw Sustained Receptor Activation and Hyperproliferation in Response to Granulocyte Colony-stimulating Factor (G-CSF) in Mice with a Severe Congenital Neutropenia/Acute Myeloid Leukemia-derived Mutation in the G-CSF Receptor Gene J. Exp. Med., February 15, 1999; 189(4): 683 - 692. [Abstract] [Full Text] [PDF] A. C. Ward, Y. M. van Aesch, A. M. Schelen, and I. P. Touw Defective Internalization and Sustained Activation of Truncated Granulocyte Colony-Stimulating Factor Receptor Found in Severe Congenital Neutropenia/Acute Myeloid Leukemia Blood, January 15, 1999; 93(2): 447 - 458. [Abstract] [Full Text] [PDF] N. Sawai, K. Koike, S. Ito, H. H. Mwamtemi, Y. Kurokawa, T. Kinoshita, K. Sakashita, T. Higuchi, K. Takeuchi, M. Shiohara, et al. Neutrophilic Cell Production by Combination of Stem Cell Factor and Thrombopoietin From CD34+ Cord Blood Cells in Long-Term Serum-Deprived Liquid Culture Blood, January 15, 1999; 93(2): 509 - 518. [Abstract] [Full Text] [PDF] N. C. Wilkinson and J. 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