Abnormal Stat activation, hematopoietic homeostasis, and innate immunity in c-fes-/- mice.
The c-fes protooncogene encodes a nonreceptor tyrosine kinase (Fes) implicated in cytokine receptor signal transduction, neutrophil survival, and myeloid differentiation. To determine the role of Fes in embryonic development and hematopoiesis, we engineered a null mutation of the murine c-fes locus. c-fes-/- mice are viable but not born in the expected Mendelian ratios. Live born c-fes-/- mice exhibit lymphoid/myeloid homeostasis defects, compromised innate immunity, and increased Stat activation in response to GM-CSF and IL-6 signaling. Therefore, increased cytokine responsiveness in the absence of Fes leads to abnormal myeloid proliferation and functional defects in the macrophage lineage.
Hackenmiller
R
R
Committee on Genetics, University of Chicago, Illinois 60637, USA.
Kim
J
J
Feldman
R A
RA
Simon
M C
MC
D000818:Animals; D001854:Bone Marrow Cells / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism; D005260:Female; D018390:Gene Targeting; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D006706:Homeostasis / Q000235:genetics* / Q000276:immunology*; D007113:Immunity, Innate / Q000235:genetics; D007153:Immunologic Deficiency Syndromes / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008221:Lymphoid Tissue / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008894:Milk Proteins; D016297:Mutagenesis, Site-Directed; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000235:genetics*; D051578:Proto-Oncogene Proteins c-fes; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000235:genetics* / Q000276:immunology*; D015534:Trans-Activators / Q000096:biosynthesis / Q000378:metabolism
D004268:DNA-Binding Proteins; D008894:Milk Proteins; D011518:Proto-Oncogene Proteins; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D011505:Protein-Tyrosine Kinases; C496646:Fes protein, mouse; D051578:Proto-Oncogene Proteins c-fes