Figure 4

Pin1-induced N3_IC downregulation prevents T-ALL development and progression in N3_IC transgenic mice. (a) CD4⁺ and/or CD8⁺ subset distribution of lymphocytes derived from SPL, PB and mesenteric lymph nodes (LM) of representative 10-week-old Pin1^+/+, N3_IC-tg and N3_IC-tg/Pin1^−/− mice. In all panels, numbers inside each cytogram indicate the percentages of the corresponding subsets and the results are representative of three independent experiments (n=3–5 mice/group: Pin1^+/+ (n=9), N3IC-tg (n=15) and N3IC-tg/Pin1^−/− mice (n=12)). (b) Splenocytes count from Pin1^+/+, N3_IC-tg and N3_IC-tg/Pin1^−/− mice at the age indicated. Values represent the means average deviations of 3–5 mice for each genetic background and P-values were calculated using Student’s T-test (i.e., **P⩽0.01; ***P⩽0.001). (c) Macroscopic aspect of SPL isolated from 20-week-old Pin1^+/+ (wt), N3_IC-tg (tg) and double mutant N3_IC-tg/Pin1^−/− (DM) mice. (d) Histological analysis of non-lymphoid organs (liver, upper and lung, down) from representative Pin1^+/+ (wt), N3_IC-tg (tg) and N3_IC-tg/Pin1^−/− (DM) mice at the age indicated. Hematoxylin and Eosin staining, original magnification × 10. (e) Mortality curve of Pin1^+/+, N3_IC-tg and N3_IC-tg/Pin1^−/− mice. The numbers of spontaneously dead mice were plotted against their age. Results are indicated as the percentage of surviving mice at each age. The follow-up of mice was stopped at 24 weeks, being 75% of the N3_IC-tg mice dead at this age and 70% of N3_IC-tg/Pin1^−/− mice survivor (n=50 for Pin1^+/+; n=60 for N3_IC-tg n=30 for N3_IC-tg/Pin1^−/− mice).