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Publication : Tissue-specific targeting of cytokine unresponsiveness in transgenic mice.

First Author  Dighe AS Year  1995
Journal  Immunity Volume  3
Issue  5 Pages  657-66
PubMed ID  7584155 Mgi Jnum  J:331605
Mgi Id  MGI:7388689 Doi  10.1016/1074-7613(95)90136-1
Citation  Dighe AS, et al. (1995) Tissue-specific targeting of cytokine unresponsiveness in transgenic mice. Immunity 3(5):657-66
abstractText  The ubiquitous cellular distribution of certain cytokine receptors has hampered attempts to define the physiologically important cell-specific functions of cytokines in vivo. Herein, we report the generation of transgenic mice that express a dominant-negative IFN gamma receptor alpha chain mutant under the control of either the human lysozyme promoter or the murine lck proximal promoter, which display tissue-specific unresponsiveness in the macrophage or T cell compartments, respectively, to the pleiotropic cytokine, IFN gamma. We utilize these mice to identify previously undefined cellular targets of IFN gamma action in the development of a murine antimicrobial response and the mixed lymphocyte reaction. Moreover, we identify the macrophage as a critical responsive cell in manifesting the effects of IFN gamma in regulating CD4+ T helper subset development. These studies thus represent a novel approach to studying the cell-specific actions of an endogenously produced pleiotropic cytokine in vivo.
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