The transferrin receptor modulates Hfe-dependent regulation of hepcidin expression.


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Schmidt, PJ; Toran, PT; Giannetti, AM; Bjorkman, PJ; Andrews, NC

Published Date

  • March 2008

Published In

Volume / Issue

  • 7 / 3

Start / End Page

  • 205 - 214

PubMed ID

  • 18316026

Pubmed Central ID

  • 18316026

International Standard Serial Number (ISSN)

  • 1550-4131

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2007.11.016


  • eng

Conference Location

  • United States