Figure 2.

Development and characterization of a mouse model of MYC-expressing medulloblastoma. A. Diagram showing the steps in model development. Mouse stem and progenitor cells were isolated from the developing mouse cerebellum and dissociated and expanded in culture. They were then transduced with lentiviruses containing c-MYC and R248WTP53 (DNp53). GFP + clones were selected and expanded for further characterization. B. Western blot showing the expression of the introduced oncogenes in the subclone used in this paper. C. Whole mount fluorescence microscopy showing the dorsal view of tumor formed by GFP-positive mCB DNp53 MYC cells, with arrowheads highlighting leptomeningeal spread of GFP + cells. A = anterior P = posterior R = right L = left D. Ventral view of the same brain, showing extensive involvement of the cerebellum with spread to the adjacent brain. E. Hematoxylin and eosin (H and E) staining at low power showing the tumor formed by mCB DNp53 MYC cells (right) adjacent to normal cerebellum (left). F. High-power H and E showing characteristics of MYC-driven medulloblastoma including abundant mitoses and apoptotic bodies, as well as large cell/anaplastic phenotype as demonstrated by prominent nucleoli and nuclear wrapping. G. IHC for MYC, showing robust expression (brown stain). Tumor cells are positive and surrounding normal cells serve as an internal negative control. H. IHC for TP53, showing robust expression (brown stain). Blood vessel at center left of panel serves as an internal negative control.