[PDF][PDF] Cre-mediated cell ablation contests mast cell contribution in models of antibody-and T cell-mediated autoimmunity

TB Feyerabend, A Weiser, A Tietz, M Stassen, N Harris… - Immunity, 2011 - cell.com
TB Feyerabend, A Weiser, A Tietz, M Stassen, N Harris, M Kopf, P Radermacher, P Möller…
Immunity, 2011cell.com
Immunological functions of mast cells remain poorly understood. Studies in Kit mutant mice
suggest key roles for mast cells in certain antibody-and T cell-mediated autoimmune
diseases. However, Kit mutations affect multiple cell types of both immune and nonimmune
origin. Here, we show that targeted insertion of Cre-recombinase into the mast cell
carboxypeptidase A3 locus deleted mast cells in connective and mucosal tissues by a
genotoxic Trp53-dependent mechanism. Cre-mediated mast cell eradication (Cre-Master) …
Summary
Immunological functions of mast cells remain poorly understood. Studies in Kit mutant mice suggest key roles for mast cells in certain antibody- and T cell-mediated autoimmune diseases. However, Kit mutations affect multiple cell types of both immune and nonimmune origin. Here, we show that targeted insertion of Cre-recombinase into the mast cell carboxypeptidase A3 locus deleted mast cells in connective and mucosal tissues by a genotoxic Trp53-dependent mechanism. Cre-mediated mast cell eradication (Cre-Master) mice had, with the exception of a lack of mast cells and reduced basophils, a normal immune system. Cre-Master mice were refractory to IgE-mediated anaphylaxis, and this defect was rescued by mast cell reconstitution. This mast cell-deficient strain was fully susceptible to antibody-induced autoimmune arthritis and to experimental autoimmune encephalomyelitis. Differences comparing Kit mutant mast cell deficiency models to selectively mast cell-deficient mice call for a systematic re-evaluation of immunological functions of mast cells beyond allergy.
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