Gab3-deficient mice exhibit normal development and hematopoiesis and are immunocompetent

Martina Seiffert, Joseph M. Custodio, Ingrid Wolf, Michael Harkey, Yan Liu, Joseph N. Blattman, Philip D. Greenberg, Larry R. Rohrschneider

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Abstract

Gab proteins are intracellular scaffolding and docking molecules involved in signaling pathways mediated by various growth factor, cytokine, or antigen receptors. Gab3 has been shown to act downstream of the macrophage colony-stimulating factor receptor, c-Fms, and to be important for macrophage differentiation. To analyze the physiological role of Gab3, we used homologous recombination to generate mice deficient in Gab3. Gab3-/- mice develop normally, are visually indistinguishable from their wild-type littermates, and are healthy and fertile. To obtain a detailed expression pattern of Gab3, we generated Gab3-specific monoclonal antibodies. Immunoblotting revealed a predominant expression of Gab3 in lymphocytes and bone marrow-derived macrophages. However, detailed analysis demonstrated that hematopoiesis in mice lacking Gab3 is not impaired and that macrophages develop in normal numbers and exhibit normal function. The lack of Gab3 expression during macrophage differentiation is not compensated for by increased levels of Gab1 or Gab2 MRNA. Furthermore, Gab3-deficient mice have no major immune deficiency in T- and B-lymphocyte responses to protein antigens or during viral infection. In addition, allergic responses in Gab3-deficient mice appeared to be normal. Together, these data demonstrate that loss of Gab3 does not result in detectable defects in normal mouse development, hematopoiesis, or immune system function.

Original languageEnglish (US)
Pages (from-to)2415-2424
Number of pages10
JournalMolecular and cellular biology
Volume23
Issue number7
DOIs
StatePublished - Apr 1 2003

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Seiffert, M., Custodio, J. M., Wolf, I., Harkey, M., Liu, Y., Blattman, J. N., Greenberg, P. D., & Rohrschneider, L. R. (2003). Gab3-deficient mice exhibit normal development and hematopoiesis and are immunocompetent. Molecular and cellular biology, 23(7), 2415-2424. https://doi.org/10.1128/MCB.23.7.2415-2424.2003