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Eur J Immunol. 2002 Sep;32(9):2653-63.

Massive inflammatory syndrome and lymphocytic immunodeficiency in KARAP/DAP12-transgenic mice.

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Centre d'Immunologie de Marseille-Luminy, CNRS-INSERM-Université de la Méditerranée, Campus de Luminy, France.


KARAP/DAP12 is a broadly distributed transmembrane signaling polypeptide with an immunoreceptor tyrosine-based activation motif, and is non-covalently associated with a variety of activating surface receptors. We report here the characterization of transgenic mice that overexpress KARAP/DAP12 polypeptides in both myeloid and lymphoid compartments. KARAP/DAP12-transgenic mice present, in a transgene dose-dependent manner, a complex phenotype characterized by two independent and spontaneous hematological abnormalities: (i) a severe lymphopenia and (ii) a massive inflammatory syndrome associated with neutrophilia and lung infiltration by multinucleated macrophages. These myeloid abnormalities observed in KARAP/DAP12-transgenic mice indicate that KARAP/DAP12-driven signals are critically involved in inflammation, and constitute an essential target to control the resolution of inflammatory disorders based on monocytes/macrophages and neutrophils.

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