title: Cre-mediated cell ablation contests mast cell contribution in models of antibody- and T cell-mediated autoimmunity.
abstract: 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.
authors.affiliation: Division for Cellular Immunology, Deutsches Krebsforschungszentrum (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Thorsten B
authors.initials: TB
authors.lastname: Feyerabend
authors.forename: Anne
authors.initials: A
authors.lastname: Weiser
authors.forename: Annette
authors.initials: A
authors.lastname: Tietz
authors.forename: Michael
authors.initials: M
authors.lastname: Stassen
authors.forename: Nicola
authors.initials: N
authors.lastname: Harris
authors.forename: Manfred
authors.initials: M
authors.lastname: Kopf
authors.forename: Peter
authors.initials: P
authors.lastname: Radermacher
authors.forename: Peter
authors.initials: P
authors.lastname: Möller
authors.forename: Christophe
authors.initials: C
authors.lastname: Benoist
authors.forename: Diane
authors.initials: D
authors.lastname: Mathis
authors.forename: Hans Jörg
authors.initials: HJ
authors.lastname: Fehling
authors.forename: Hans-Reimer
authors.initials: HR
authors.lastname: Rodewald
mesh_terms: D000707:Anaphylaxis / Q000235:genetics / Q000276:immunology; D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D043422:Carboxypeptidases A / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology; D020869:Gene Expression Profiling; D018390:Gene Targeting; D020022:Genetic Predisposition to Disease; D007073:Immunoglobulin E / Q000276:immunology; D019426:Integrases / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019089:Stem Cell Factor / Q000172:deficiency; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D019089:Stem Cell Factor; D016159:Tumor Suppressor Protein p53; D007073:Immunoglobulin E; C045073:Cre recombinase; D019426:Integrases; D043422:Carboxypeptidases A; C503326:Cpa3 protein, mouse