Enforced expression of c-Myc and T58A-mutant c-Myc in adult thymic epithelial cell subsets

Abstract

Abstract Thymic epithelial cells (TEC) are essential for T lymphopoiesis. Cortical (c)TEC support T lineage commitment and positive selection, whereas medullary (m)TEC delete self-reactive T cells to enforce central tolerance. Both cTEC and mTEC contain several distinct subtypes that were only recently characterized, and precursor-progeny relationships among adult TEC remains incompletely understood. Prior work in our lab demonstrated that enforced expression of c-Myc broadly in TEC under a constitutive FoxN1-Cre increased thymus size and TEC numbers, while maintaining morphology and function. To elucidate which TEC subtypes require enforced c-Myc expression to drive thymic expansion in adults, we’ve developed and acquired Cre-ERT2 systems under the control of TEC-specific genes FoxN1, Aire, and Ccl21a. This allows us to target expression of c-Myc or stabilized T58A-mutant c-Myc to specific subsets of TEC in adult mice. Analysis of these systems is currently ongoing and results will be presented. We hypothesize that enforced expression of c-Myc or stabilized T58A-mutant c-Myc in specific adult TEC subsets will expand the targeted population and may eventually result in transformation. Regardless of whether our hypothesis is correct, our experiments will contribute to better understanding of c-Myc-driven thymic hyperplasia and may provide a mouse model for human thymoma.