Mast cells genetics

The in vivo relevance and biological importance of in vitro observations about mast cell function, as well as the contributions of mast cells towards the expression of particular biological responses (such as various models of anaphylaxis) in vivo, can be assessed using c-kit mutant mice (e.g., WBB6Fi-FCit or mice) that virtually lack mast cell populations. Mice with mutations of c-kit [6,11] or mutations that affect KIT expression [12-14] have other abnormalities of phenotype besides a mast cell deficiency. However, the mast cell deficiency of these mice can be selectively repaired by the adoptive transfer of genetically compatible, in vitro-derived... 

It is generally accepted (based on clinical and in vitro studies) that mast cells (and basophils), IgE and FceRI are involved in most cases of allergen-induced anaphylaxis in humans. However, it is difficult to define the exact roles and relative importance of mast cells, basophils, and other potential effector cells (e.g monocytes/macrophages, dendritic cells) in either IgE-dependent or IgE-independent human anaphylaxis. Unlike in mice, we neither have access to mast cell- or basophil-deficient humans nor can we genetically manipulate human subjects to produce such phenotypes. 

Nigrovic PA, Gray DH. Jones T. Hallgren J, Kuo EC, Chaletzky B, Gurish M. Mathis D. Benoist C, Lee DM genetic inversion in mast cell-deficient W mice interrupts Cortn and manifests as hematopoietic and cardiac aberrancy. Am J Pathol 2008 173 1693-16701. 

Atopic dermatitis is an inflammatory condition with genetic, environmental, and immunologic mechanisms. Many immune cells have demonstrated abnormalities, including Langerhans cells, monocytes, macrophages, lymphocytes, mast cells, and keratinocytes. 

The onset of asthma might depend on both genetic and environmental components. In childhood the expression of IFN-7 is fundamental in determining the future T-cell development. In fact, defective IFN-7 early in life favors a Th2 cell development probably as a result of increased IL-6 production by DCs or mast cells and/or IL-4 production by natural killer or other cells. The increased GATA-3 expression in the lung of asthmatics points in this direction. The defect in T-bet or its genetic modification in asthmatics underlines the... 

Sonoda, T., Kitamura, Y., Haku, Y., Hara, H. and Mori, K.J. (1984). Proliferation of peritoneal mast cells in the skin of W/Wv mice that genetically lack mast cells. J. Exp. Med. 160, 138-151. 

Wershil, B.K., Mekori, Y.A., Murakami, T. and Galli, S.J. (1987). 1251-fibrin deposition in IgE-dependent immediate hypersensitivity reactions in mouse skin. Demonstration of the role of mast cells using genetically mast cell-deficient mice locally reconstituted with cultured mast cells. J. Immunol. 139, 2605-2614. 

Chong LK, Chowdry J, Ghahramani P, Peachell PT. Influence of genetic polymorphisms in the p2-adrenoceptor on desensitization in human lung mast cells. Pharmacogenetics 1999 10 153-162. 

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