Patients suffering from hereditary
hemochromatosis (HH) show progressive
iron overload as a consequence of increased duodenal
iron absorption. It has been hypothesized that mutations in the HH gene HFE cause misprogramming of the duodenal enterocytes towards a paradoxical
iron-deficient state, resulting in increased
iron transporter expression. Previous reports concerning gene expression levels of the duodenal
iron transporters DMT1 and IREG1 in HH patients and animal models are controversial, however, and in many cases only
mRNA expression levels were investigated. To analyze the duodenal expression of DMT1, Ireg1, Dcytb, and hephaestin and the association with
iron overload in adult Hfe(-/-) mice, an Hfe(-/-) mouse line was generated. Duodenal DMT1 and Ireg1
protein levels, duodenal DMT1, Ireg1, Dcytb, hephaestin, and TfR1
mRNA levels, and hepatic
hepcidin mRNA levels were quantified and the correlation to liver
iron contents was calculated. We report that duodenal DMT1 and Ireg1
mRNA levels and DMT1 and Ireg1
protein levels remained unaffected by the Hfe deletion. Furthermore, duodenal hephaestin and TfR1
mRNA expression and hepatic
hepcidin mRNA expression remained unaltered, while the duodenal
mRNA expression of the brush border
ferric reductase Dcytb was significantly increased in Hfe(-/-) mice. We found no correlation between the expression level of any of the analyzed transcripts and the liver
iron content. In conclusion, the lack of correlation between DMT1 and Ireg1
protein expression and the liver
iron content suggests that elevated duodenal
iron transporter expression is not required for high liver
iron overload. Hfe(-/-) mice do not necessarily display features of
iron deficiency in the duodenum, indicated by an increase in
mRNA and
protein levels of DMT1 and Ireg1. Rather, the duodenal
ferric reductase Dcytb may act as a possible mediator of
iron overload in Hfe deficiency.