Attenuation of elevated CDC42 activity ensures survival. (A) Serial IP injection of 5-FU in the following genotypes: CTRL: O5A^+/+ n = 6, 5A^fl/fl n = 7 and O5A^Δ/Δ n = 7 at day 0 and day 8. Additional in vivo IP injection of CDC42-GTP inhibitor CASIN at day 5 through day 8. Analysis of animal survival, hematopoiesis (BM from 4 flushed long bones), and compact bone-derived MSPCs at day 14. (B) Percentage of mice survival after serial 5-FU treatment. Graph shows the survival curve of CTRL and O5A^Δ/Δ mice treated with CASIN (+) or vehicle (-). (C) Graph shows the total BM cell number (left) and relative number of LSK cells (middle) and MPs (right) at day 14 of CTRL mice with vehicle ([-]; O5A^+/+ n = 6, 5A^fl/fl n = 7), O5A^Δ/Δ mice with vehicle ([-]; n = 5, mice analyzed shortly before death) and O5A^Δ/Δ mice with CASIN ([+]; n = 5). (D,F,H,J) Representative contour plots from BM populations. Graphs show relative number of LT-HSCs and ST-HSCs (E-F), T cells and B cells (G-H), and Gr1⁺ myeloid cells (I-J). *P < .05 (nonparametric Mann-Whitney test: C,E,G,I). The results represent 2 to 3 independent experiments. Data are represented as mean ± SEM. Symbol legend shown in Figure 6A.