In-line with previous studies showing that defects in the HFE and TfR2 proteins (and their combination) upstream from hepcidin synthesis resulted in low circulating hepcidin levels [22]–[27], our 3 mouse hemochromatosis models all showed impaired Hep-1 production, being most prominently present in double affected Hfe/TfR2y245x mice. This evidence concerns the gene HAMP and hemochromatosis.