Abnormal Stat activation, hematopoietic homeostasis, and innate immunity in c-fes-/- mice

Immunity. 2000 Sep;13(3):397-407. doi: 10.1016/s1074-7613(00)00039-x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bone Marrow Cells / enzymology
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / pathology
  • Cell Adhesion / genetics
  • Cell Adhesion / immunology
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cell Division / genetics
  • Cell Division / immunology
  • Cells, Cultured
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / metabolism
  • Female
  • Gene Targeting
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Hematopoietic Stem Cells / enzymology*
  • Hematopoietic Stem Cells / immunology*
  • Hematopoietic Stem Cells / pathology
  • Homeostasis / genetics*
  • Homeostasis / immunology*
  • Immunity, Innate / genetics
  • Immunologic Deficiency Syndromes / enzymology
  • Immunologic Deficiency Syndromes / genetics
  • Immunologic Deficiency Syndromes / metabolism
  • Immunologic Deficiency Syndromes / pathology
  • Lymphoid Tissue / enzymology
  • Lymphoid Tissue / immunology
  • Lymphoid Tissue / pathology
  • Macrophages / enzymology
  • Macrophages / immunology
  • Macrophages / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Milk Proteins*
  • Mutagenesis, Site-Directed
  • Protein-Tyrosine Kinases*
  • Proto-Oncogene Proteins / deficiency*
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-fes
  • STAT3 Transcription Factor
  • STAT5 Transcription Factor
  • Signal Transduction / genetics*
  • Signal Transduction / immunology*
  • Trans-Activators / biosynthesis
  • Trans-Activators / metabolism

Substances

  • DNA-Binding Proteins
  • Milk Proteins
  • Proto-Oncogene Proteins
  • STAT3 Transcription Factor
  • STAT5 Transcription Factor
  • Stat3 protein, mouse
  • Trans-Activators
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Protein-Tyrosine Kinases
  • Fes protein, mouse
  • Proto-Oncogene Proteins c-fes