A Knock-in Mouse Model of Thymoma with the GTF2I L424H Mutation

We previously identified a recurrent mutation L424H in the transcription factor GTF2I in thymic epithelial tumors. The precise role of the GTF2I mutation in these tumors is unclear. Here we describe the generation and characterization of a mouse model in which the Gtf2i L424H mutation was conditionally knocked-in in the Foxn1+ thymic epithelial cells. The Gtf2i mutation impairs development of thymic medulla and maturation of medullary thymic epithelial cells in the young mice and causes tumor formation in the thymus of the aged KI mice. To characterize the molecular features of murine thymomas, we performed digital spatial profiling with GeoMx moue whole transcriptome atlas assay with FFPE thymic tissues of 4 KI and 4 control mice. FFPE thymic tissues of 4 Gtf2i L424H mutation KI and 4 control mice were profiled with the GeoMx whole transcriptome atlas assay. 60 regions were chosen, 95 ROIs were collected from the selected regions based on the expression of markers. They include the epithelial cells (PanCK+), T cells (CD3+), and B cells (B220+) ROIs.