Evaluation of the role of the basic helix-loop-helix transcription factor twist-2 in lymphocyte development and activation

Transcription factors belonging to the basic Helix-Loop-Helix (bHLH) family have been shown to regulate a variety of signaling pathway and the development and activity of numerous cell types. The bHLH transcription factor Twist-2 is known to be a potent suppressor of NF-kappaB signaling in several processes including hematopoiesis. In previous research a Twist-2 conventional knockout mouse was found to have a dramatic phenotype including increased myeloid lineage, inflammatory cytokine increase and death shortly after birth. NF-kappaB signaling has been shown to be crucial for development and activation of lymphocytes, so we hypothesize that Twist-2 may play a role in lymphocyte development and function. The generation and initial characterization of a novel colony of tissue specific Twist-2 knockout mouse created by breeding Twist-2floxed mice with MMTVcre mice is described here. Twist-2fl/fl; MMTVcre mice display no gross dysmorphism and are fertile. Initial characterization of thymocytes from these mice has been performed using flow cytometry analysis of peripheral blood, thymus, lymph node and spleen. Splenic T cells from these mice demonstrated decreased proliferation in an ex Vivo proliferation assay. Preliminary observations suggest that Twist-2 may influence T cell development or activation.