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

The X-linked inhibitor of apoptosis (XIAP) and other members of the inhibit or of apoptosis (IAP) family can suppress apoptosis induced by a diverse va riety of triggers. Functional studies done to date have focused on tissue c ulture models and adenovirus overexpression of XIAP and other IAP proteins. Here we report the phenotype of an engineered transgenic mouse overexpress ing a human IAP. as well as assessing the long-term consequence of IAP over expression, We document the relative protein expression levels of the endog enous mouse homologue to XIAP, mouse inhibitor of apoptosis (MIAP 3), withi n thymocyte and T cell subpopulations, The consequence of lymphoid-targeted overexpression of XIAP in transgenic mice suggests a physiological role fo r the endogenous protein, MIAP3, Xiap-transgenic mice accumulated thymocyte s and/or T cells in primary and secondary lymphoid tissue, T cell maturatio n 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 home ostasis of the immune system.