Acute and chronic hypoxia triggers erythropoietic responses in P3Pro mutants. (A) In P3Pro mutant mice a linear decline in the Hct value is associated with an exponential increase in serum Epo levels in response to acute anemic hypoxia (R² = 0.60, P < .0001). Linear regression analysis showed no statistically significant difference between slopes of increase in P3Pro mutants and control mice. Serum Epo levels were measured 24 hours after phlebotomy. (B) Exposure of P3Pro mutant mice to chronic normobaric hypoxia (10% O₂ for 10 days) increases Hct values. (Bottom) The serum Epo levels shown in P3Pro mutant (n = 11) and in control mice (n = 12), were measured after 10 days of hypoxia. (C) Prolyl-4-hydroxylase inhibition with GSK1002083A raises Hct values and serum Epo levels in P3Pro mutants. Shown are Hct values before treatment (day 0) and after 10 days of treatment (day 10). Serum Epo levels in P3Pro mutants were measured 4 hours after administration of 2 doses (n = 3). Vehicle indicates treatment with 1% methylcellulose without compound; PHI, treatment with PHD inhibitor GSK 1002083A. **P < .01, ***P < .001.