title: CreER(T2) expression from within the c-Kit gene locus allows efficient inducible gene targeting in and ablation of mast cells.
abstract: Mast cells are abundantly situated at contact sites between the body and its environment, such as the skin and, especially during certain immune responses, at mucosal surfaces. They mediate allergic reactions and degrade toxins as well as venoms. However, their roles during innate and adaptive immune responses remain controversial and it is likely that major functions remain to be discovered. Recent developments in mast cell-specific conditional gene targeting in the mouse promise to enhance our understanding of these fascinating cells. To complete the genetic toolbox to study mast cell development, homeostasis and function, it is imperative to inducibly manipulate their gene expression. Here, we report the generation of a novel knock-in mouse line expressing a tamoxifen-inducible version of the Cre recombinase from within the endogenous c-Kit locus. We demonstrate highly efficient and specific inducible expression of a fluorescent reporter protein in mast cells both in vivo and in vitro. Furthermore, induction of diphtheria toxin A expression allowed selective and efficient ablation of mast cells at various anatomical locations, while other hematopoietic cells remain unaffected. This novel mouse strain will hence be very valuable to study mast cell homeostasis and how specific genes influence their functions in physiology and pathology.
authors.affiliation: Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Heger
authors.forename: Barbara
authors.initials: B
authors.lastname: Seidler
authors.forename: J Christoph
authors.initials: JC
authors.lastname: Vahl
authors.forename: Christian
authors.initials: C
authors.lastname: Schwartz
authors.forename: Maike
authors.initials: M
authors.lastname: Kober
authors.forename: Sabine
authors.initials: S
authors.lastname: Klein
authors.forename: David
authors.initials: D
authors.lastname: Voehringer
authors.forename: Dieter
authors.initials: D
authors.lastname: Saur
authors.forename: Marc
authors.initials: M
authors.lastname: Schmidt-Supprian
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D004167:Diphtheria Toxin / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D055879:Gene Knock-In Techniques; D018390:Gene Targeting / Q000379:methods*; D056426:Genetic Loci / Q000235:genetics; D019426:Integrases / Q000235:genetics / Q000378:metabolism*; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic / Q000276:immunology*; D009928:Organ Specificity; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D013629:Tamoxifen / Q000008:administration & dosage; D019076:Transgenes / Q000235:genetics
chemical_list: D004167:Diphtheria Toxin; D010446:Peptide Fragments; C029795:diphtheria toxin fragment A; D013629:Tamoxifen; D019009:Proto-Oncogene Proteins c-kit; C045073:Cre recombinase; D019426:Integrases
keywords: Inducible conditional gene targeting; Mast cells; c-Kit locus