Effect of FG-4497 on blood hemoglobin, hematocrit, and reticulocyte values 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 (*P < .02 for reticulocytes in panel A and C, P = .05 for hematocrit in panel C, **P < .005). The differences between the values for the FG-4497–treated and vehicle-treated mice are significant or highly significant for all hemoglobin and hematocrit values in panels A through C as follows. Comparison of FG-4497–treated wild-type mice with vehicle-treated wild-type mice: in panel A hemoglobin and hematocrit at 3 and 5 weeks P < .001; in panel B hemoglobin P < .05, hematocrit P < .001; in panel C hemoglobin at 3 weeks P = .056, at 4 weeks P < .02 and at 5 weeks P < .001, hematocrit at 3 weeks P < .005 and at 4 and 5 weeks P < .001; comparison of FG-4497–treated gene-modified mice with vehicle-treated gene-modified mice: (A) hemoglobin and hematocrit at 3 weeks P < .02, at 5 weeks P < .001; (B) hemoglobin and hematocrit P < .001; (C) hemoglobin and hematocrit at 3 weeks P < .005 and at 4 and 5 weeks P < .001. Similar comparisons of reticulocyte values are as follows. Comparison of FG-4497–treated wild-type mice with vehicle-treated wild-type mice: in panel A at 3 weeks P < .005, in panel C at 3 weeks P < .05 and at 4 weeks P < .001; comparison of FG-4497–treated gene-modified mice with vehicle-treated gene-modified mice in panel A at 3 weeks P < .002, in panel C at 3 weeks P < .05 and at 4 weeks P < .001. There are no significant differences between the values for the vehicle-treated gene-modified and wild-type mice in panels A through C. Values of n as in Figure 3. Error bars represent SEM.