Effect of repeated FG-4497 doses on serum Epo concentration in P4h-tm null, Hif-p4h-2 hypomorphic, and Hif-p4h-3 null mice. The P4h-tm^−/− (A), Hif-p4h-2^gt/gt (B), and Hif-p4h-3^−/− (C) mice and wild-type mice received 3 oral doses of FG-4497 (100 mg/kg) per week for 3 to 5 weeks and were killed 6 hours after the last dose. Statistical significance is shown only for the comparison of the values between the FG-4497–treated gene-modified and wild-type mice, the means of the latter being taken as 100% (*P < .05, **P < .01, ***P < .0001). There are no significant differences between the values for the vehicle-treated gene-modified and wild-type mice in panels A through C, whereas the differences between the values for the FG-4497–treated and vehicle-treated mice are highly significant in panels A through C. In panel A, n = 5 for all groups at 3 weeks, n = 13 for the FG-4497–treated wild-type mice and n = 6 for the FG-4497–treated P4h-tm^−/− mice at 5 weeks; in panel B n = 6-8 for all groups; and in panel C n = 4 for each group at 3 weeks, n = 5 and n = 16-18 for the 2 FG-4497–treated groups at 4 and 5 weeks, respectively. Error bars represent SEM.