title: Induced Syk deletion leads to suppressed allergic responses but has no effect on neutrophil or monocyte migration in vivo.
abstract: The spleen tyrosine kinase (Syk) is a key mediator of immunoreceptor signaling in immune cells. Thus, interfering with the function of Syk by genetic deletion or pharmacological inhibition might influence a variety of allergic and autoimmune processes. Since conventional Syk knockout mice are not viable, studies addressing the effect of Syk deletion in adult animals have been limited. To further explore functions of Syk in animal models of allergy and to shed light on the role of Syk in the in vivo migration of neutrophils and monocytes, we generated inducible Syk knockout mice. These mice harbor a floxed Syk gene and a tamoxifen-inducible Cre recombinase under the control of the ubiquitously active Rosa26-promoter. Thus, treatment of mice with tamoxifen leads to the deletion of Syk in all organs. Syk-deleted mice were analyzed in mast cell-dependent models and in models focusing on neutrophil and monocyte migration. We show that Syk deletion in adult mice reduces inflammatory responses in mast cell-driven animal models of allergy and asthma but has no effect on the migration of neutrophils and monocytes. Therefore, the inducible Syk knockout mice presented here provide a valuable tool to further explore the role of Syk in disease-related animal models.
authors.affiliation: Department of Respiratory Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Wex
authors.forename: Thierry
authors.initials: T
authors.lastname: Bouyssou
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Duechs
authors.forename: Klaus J
authors.initials: KJ
authors.lastname: Erb
authors.forename: Florian
authors.initials: F
authors.lastname: Gantner
authors.forename: Michael P
authors.initials: MP
authors.lastname: Sanderson
authors.forename: Andreas
authors.initials: A
authors.lastname: Schnapp
authors.forename: Birgit E
authors.initials: BE
authors.lastname: Stierstorfer
authors.forename: Lutz
authors.initials: L
authors.lastname: Wollin
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement; D002469:Cell Separation; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D005434:Flow Cytometry; D006967:Hypersensitivity / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology*; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D009504:Neutrophils / Q000166:cytology / Q000276:immunology*; D011505:Protein-Tyrosine Kinases / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D000072377:Syk Kinase
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse