Transgenic Models in Allergic Responses

Author(s): Michael Hausding, Kerstin Sauer, Joachim H. Maxeiner, Susetta Finotto

Journal Name: Current Drug Targets

Volume 9 , Issue 6 , 2008

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The immunoresponses are mediated by cells presenting the antigen to T cells. The transcription factors involved in the differentiation of T helper cells enclose T-bet (Th1), c-maf (Th2), GATA-3 (Th2), Foxp3 (T reg) and RORγT (Th17). They are regulated in allergic asthma. The use of murine models either as germline or as tissue specific transgenic mice has given decisive immunological tools to understand the importance of selected transcription factors or cytokines. Tissue specific transgenic lines have been generated into the Clara Cell or CD2 promoter directing tissue- and immune cells specific expression of the gene of interest. We identified T cell transcription factors important for asthma – such as T-bet, c-maf, GATA-3. Transgenic and knockout murine models of these transcription factors provided very important information for the human disease. Regarding to the pathogenesis of chronic asthma, we generated transgenic lines overexpressing IL-18 and analyzed a dominant negative mutant of the TGF-β receptor II. These models will offer to us a great input for the understanding of the T cell memory and the processes like airway remodelling. Beside DNA microinjection and stem cell transfer the On/Off systems like Cre-lox models have helped to understand the role of selected genes in different steps of experimental disease. Moreover, the transgenic model provide reliable models for the preclinical approval of therapy for allergic asthma to develop more efficient compounds and functional antibodies.

Keywords: Transgenic mice, allergic asthma, T regulatory cells, CD2 promoter, T-bet, TGF-β1

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Article Details

Year: 2008
Page: [503 - 510]
Pages: 8
DOI: 10.2174/138945008784533570
Price: $65

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