Open AccessEnhanced Endotoxin Sensitivity in Fps/Fes-Null Mice with Minimal Defects in Hematopoietic Homeostasis
Author(s) -
Ralph Zirngibl,
Yotis A. Senis,
Peter A. Greer
Publication year - 2002
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.22.8.2472-2486.2002
Subject(s) - biology , myelopoiesis , haematopoiesis , myeloid , bone marrow , microbiology and biotechnology , progenitor cell , cancer research , stat protein , innate immune system , immunology , signal transduction , stat3 , immune system , stem cell
The fps/fes proto-oncogene encodes a cytoplasmic protein tyrosine kinase implicated in growth factor and cytokine receptor signaling and thought to be essential for the survival and terminal differentiation of myeloid progenitors. Fps/Fes-null mice were healthy and fertile, displayed slightly reduced numbers of bone marrow myeloid progenitors and circulating mature myeloid cells, and were more sensitive to lipopolysaccharide (LPS). These phenotypes were rescued using a fps/fes transgene. This confirmed that Fps/Fes is involved in, but not required for, myelopoiesis and that it plays a role in regulating the innate immune response. Bone marrow-derived Fps/Fes-null macrophages showed no defects in granulocyte-macrophage colony-stimulating factor-, interleukin 6 (IL-6)-, or IL-3-induced activation of signal transducer and activator of transcription 3 (Stat3) and Stat5A or LPS-induced degradation of I kappa B or activation of p38, Jnk, Erk, or Akt.