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 cellspecific 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 tamoxifeninducible 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.
Keywords: c-Kit locus r Inducible conditional gene targeting r Mast cellsAdditional supporting information may be found in the online version of this article at the publisher's web-site
IntroductionMast cells belong to the innate arm of the immune system and mediate immunoglobulin E (IgE)-associated reactions. CrossCorrespondence: Dr. Marc Schmidt-Supprian e-mail: supprian@biochem.mpg.de linking of their high affinity IgE receptor (FcεRI) leads to secretion of preformed granule associated mediates such as vasoactive amines and proteases, and to de novo synthesis of proinflammatory lipid mediators and cytokines [1]. In addition, several reports * These authors contributed equally to this work.C 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2014. 44: 296-306 New technology 297 attest mast cells numerous IgE-independent effector and regulatory functions in innate and adaptive immune responses against bacteria and pathogens [2-4], autoimmunity [5][6][7], tolerance induction [8][9][10], obesity and diabetes [11], contact hypersensitivity [12], angiogenesis, and malignant diseases [13]. Most in vivo evidence for these functions relies on the use of mice lacking mast cells mainly due to various spontaneous loss-of-function mutations in the white-spotting (W) locus that encodes for the receptor tyrosine kinase c-Kit [14][15][16][17]. However, recent experiments using c-Kit-independent mast cell-deficient mice have failed to corroborate some of these initial findings [18][19][20]. While the exact reasons for these discrepant results remain unclear, it appears obvious that the further elucidation of in vivo mast cell functions will benefit from novel...