Overexpression of the Wiskott-Aldrich syndrome protein N-terminal domain in transgenic mice inhibits T cell proliferative responses via TCR signaling without affecting cytoskeletal rearrangements.

摘要: Wiskott-Aldrich syndrome (WAS) is an X-linked recessive disorder characterized by thrombocytopenia with small platelets, severe eczema, and recurrent infections due to defects in the immune system. The disease arises from mutations gene encoding WAS protein (WASP), which plays a role as adaptor molecule signal transduction accompanied cytoskeletal rearrangement T cells. To investigate functional domain of WASP, we developed transgenic mice overexpressing WASP N-terminal region (exon 1–5) including Ena/VASP homology 1 (pleckstrin homology/WASP 1) domain, majority patients have been observed. develop grow normally under specific pathogen-free environment, showed normal lymphocyte development. However, proliferative responses cytokine production induced TCR stimulation were strongly inhibited mice, whereas Ag receptor capping actin polymerization normal. These findings suggest that overexpressed inhibits signaling without coupling rearrangement. shown here could be valuable tools for further understanding WASP-mediated processes.