Figure 3.
Low expression levels of key BA-producing enzymes predict poor recovery in mice. (A) The experimental setup of 5-FU treatment in Cyp8b1 KO mice. Heterozygous mice showing low messenger RNA expression levels of both Cyp7a1 and Cyp8b1 (0.01-fold compared with WT mice) were categorized as HT-low. (B) Expression of key BA-producing enzymes in Cyp8b1 KO mice. Gene expression levels relative to Actb are shown (n = 10-30). (C) TBA levels measured in plasma of Cyp8b1 KO mice on day 8 after 5-FU treatment. Fold change relative to WT/HT is shown (n = 7-26). (D-F) Cellularity in PB of WT/HT or HT-low mice on day 8 after 5-FU treatment. Total cellularity (D), myeloid cells (E), and lymphoid cells (F) are shown (n = 8-34). (G-I) Cellularity in BM of WT/HT or HT-low mice on day 8 after 5-FU treatment. Total cellularity (G), myeloid cells (H), and lymphoid cells (I) in femur and tibia are shown (n = 8-34). (J-L) Cellularity of primitive cells in BM of WT/HT or HT-low mice after 5-FU treatment. Lineage− cells (J), c-kit+ cells (K), and HSCs (defined as CD150+CD48−c-kit+Sca-I+lineage− cells) (L) in femur and tibia are shown (n = 8-34). (M) BA composition in recovery on day 8 after 5-FU injection (n = 7-24). Results are presented as means ± SEM. *P < .05; **P < .01; ***P < .001; ****P < .0001.