| First Author | Schmidt PJ | Year | 2008 |
| Journal | Cell Metab | Volume | 7 |
| Issue | 3 | Pages | 205-14 |
| PubMed ID | 18316026 | Mgi Jnum | J:133221 |
| Mgi Id | MGI:3778114 | Doi | 10.1016/j.cmet.2007.11.016 |
| Citation | Schmidt PJ, et al. (2008) The transferrin receptor modulates Hfe-dependent regulation of hepcidin expression. Cell Metab 7(3):205-14 |
| abstractText | Hemochromatosis is caused by mutations in HFE, a protein that competes with transferrin (TF) for binding to transferrin receptor 1 (TFR1). We developed mutant mouse strains to gain insight into the role of the Hfe/Tfr1 complex in regulating iron homeostasis. We introduced mutations into a ubiquitously expressed Tfr1 transgene or the endogenous Tfr1 locus to promote or prevent the Hfe/Tfr1 interaction. Under conditions favoring a constitutive Hfe/Tfr1 interaction, mice developed iron overload attributable to inappropriately low expression of the hormone hepcidin. In contrast, mice carrying a mutation that interferes with the Hfe/Tfr1 interaction developed iron deficiency associated with inappropriately high hepcidin expression. High-level expression of a liver-specific Hfe transgene in Hfe-/- mice was also associated with increased hepcidin production and iron deficiency. Together, these models suggest that Hfe induces hepcidin expression when it is not in complex with Tfr1. |
