Alk2 and Alk3 are essential for iron-dependent hepcidin regulation in vivo. Eight-week-old mice were challenged intravenously with dextran (as a control) or iron-dextran (Fe; 0.2 mg/kg). (A) Hepatic hepcidin mRNA levels in Alk2^fl/fl and Alk2^fl/fl; Alb-Cre mice (n ≥ 6 per group). *P < .0001, Alk2^fl/fl mice challenged with dextran versus Alk2^fl/fl mice challenged with iron-dextran. (B) Hepatic hepcidin mRNA levels in similarly challenged Alk3^fl/fl and Alk3^fl/fl; Alb-Cre mice (n ≥ 3 per group). *P < .0045, versus Alk3^fl/fl mice challenged with dextran versus Alk3^fl/fl mice challenged with iron-dextran. ^#P < .005, Alk2^fl/fl; Alb-Cre mice challenged with dextran versus Alk3^fl/fl mice challenged with dextran.