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Publication : Thymocyte-targeted overexpression of xiap transgene disrupts T lymphoid apoptosis and maturation.

First Author  Conte D Year  2001
Journal  Proc Natl Acad Sci U S A Volume  98
Issue  9 Pages  5049-54
PubMed ID  11309492 Mgi Jnum  J:128833
Mgi Id  MGI:3768065 Doi  10.1073/pnas.081547998
Citation  Conte D, et al. (2001) Thymocyte-targeted overexpression of xiap transgene disrupts T lymphoid apoptosis and maturation. Proc Natl Acad Sci U S A 98(9):5049-54
abstractText  The X-linked inhibitor of apoptosis (XIAP) and other members of the inhibitor of apoptosis (IAP) family can suppress apoptosis induced by a diverse variety of triggers. Functional studies done to date have focused on tissue culture models and adenovirus overexpression of XIAP and other IAP proteins. Here we report the phenotype of an engineered transgenic mouse overexpressing a human IAP, as well as assessing the long-term consequence of IAP overexpression. We document the relative protein expression levels of the endogenous mouse homologue to XIAP, mouse inhibitor of apoptosis (MIAP 3), within thymocyte and T cell subpopulations. The consequence of lymphoid-targeted overexpression of XIAP in transgenic mice suggests a physiological role for the endogenous protein, MIAP3. Xiap-transgenic mice accumulated thymocytes and/or T cells in primary and secondary lymphoid tissue, T cell maturation was perturbed, and transgenic thymocytes resisted a variety of apoptotic triggers both in vitro and in vivo. These observations imply a possible key function for the intrinsic cellular inhibitor XIAP in maintaining the homeostasis of the immune system.
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