Massive inflammatory syndrome and lymphocytic immunodeficiency in KARAP/DAP12-transgenic mice.
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.
Centre d'Immunologie de Marseille-Luminy, CNRS-INSERM-Université de la Méditerranée, Campus de Luminy, France.
Mathias
M
Lucas
Laurent
L
Daniel
Elena
E
Tomasello
Sophie
S
Guia
Nicole
N
Horschowski
Naoko
N
Aoki
Dominique
D
Figarella-Branger
Sophie
S
Gomez
Eric
E
Vivier
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006410:Hematopoiesis; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000473:pathology; D008221:Lymphoid Tissue / Q000378:metabolism / Q000473:pathology; D008231:Lymphopenia / Q000235:genetics* / Q000473:pathology; D008264:Macrophages / Q000473:pathology*; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009504:Neutrophils / Q000473:pathology*; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012772:Shock, Septic / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D019282:Wasting Syndrome / Q000235:genetics / Q000473:pathology
D048868:Adaptor Proteins, Signal Transducing; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D011971:Receptors, Immunologic; C110546:TYROBP protein, human