Strain susceptibility to GDX-induced adrenocortical neoplasia is cell intrinsic and resides in the stem/progenitor cell compartment. A chimeric mouse was generated by injecting Rosa26-GFP XY embryonic stem cells from a non-susceptible strain (B6) into an XY blastocyst from a susceptible strain (B6D2F1). The mouse was gonadectomized at 3 weeks of age, and adrenal glands were harvested 5 mo later. Adjacent cryosections of adrenal tissue were stained with H&E (A,C) or examined by fluorescence microscopy (B,D). Note that normal adrenocortical cells can arise from either GFP+ B6 progenitors or GFP− B6D2F1 progenitors (alternating stripes in panel B), whereas the neoplastic cells are derived exclusively from B6D2F1 progenitors. In this mouse, 4 separate tumors were identified; each was derived exclusively from B6D2F1 tissue. Bars = 50 µm.