Figure 4: Effects of Myc inhibition in the brain of GFAP-V¹²Ha-Ras symptomatic mice.

(a) Symptomatic triple transgenic TRE-Omomyc;CMVrtTA;GFAP-V¹²Ha-Ras mice were treated with doxycycline for 7 days (n=2) or untreated (n=3). Histological analysis (left panels) shows a reduction in Ki67 positive (proliferating) cells and an increase in dying TUNEL-positive cells in Omomyc-expressing mice. (b) Quantification of the Ki67 positivity from the histological analysis in a. The percentage of proliferating cells is shown in the graph, and the total number of cells counted in five fields is also indicated in the table. (c) Quantification of the TUNEL positivity from the histological analysis described above. The percentage of TUNEL-positive cells is shown in the graph, and the total number of cells counted in five fields is also indicated in the table. (d) Omomyc treatment causes the appearance of multinucleated cells. Symptomatic triple transgenic TRE-Omomyc;CMVrtTA;GFAP-V¹²Ha-Ras mice were treated with doxycycline for 7 days. Histological analysis was performed on isolated brains to look for GFAP-positive astrocytes in tumour regions (green dye). Nuclei were counterstained with Hoechst (coloured pink here after merging with the GFAP images to facilitate visualization of the nuclei). (e) Quantification of the number of multinucleated GFAP-positive nuclei after Omomyc treatment (n=2) for 7 days compared with untreated mice (n=2). The average of two mice is shown+s.e. For each mouse, a minimum of 10 microscopic fields and 300 cells were scored. Data are shown as means+s.e. P-value was calculated by Student’s t-test.