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The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis.

Cell metabolism | Mar 1, 2005

http://www.ncbi.nlm.nih.gov/pubmed/16054062

Ferroportin (SLC40A1) is an iron transporter postulated to play roles in intestinal iron absorption and cellular iron release. Hepcidin, a regulatory peptide, binds to ferroportin and causes it to be internalized and degraded. If ferroportin is the major cellular iron exporter, ineffective hepcidin function could explain manifestations of human hemochromatosis disorders. To investigate this, we inactivated the murine ferroportin (Fpn) gene globally and selectively. Embryonic lethality of Fpn(null/null) animals indicated that ferroportin is essential early in development. Rescue of embryonic lethality through selective inactivation of ferroportin in the embryo proper suggested that ferroportin has an important function in the extraembryonic visceral endoderm. Ferroportin-deficient animals accumulated iron in enterocytes, macrophages, and hepatocytes, consistent with a key role for ferroportin in those cell types. Intestine-specific inactivation of ferroportin confirmed that it is critical for intestinal iron absorption. These observations define the major sites of ferroportin activity and give insight into hemochromatosis.

Pubmed ID: 16054062 RIS Download

Mesh terms: Animals | Cation Transport Proteins | Embryo, Mammalian | Endoderm | Enterocytes | Hepatocytes | Homeostasis | Intestinal Absorption | Iron | Macrophages | Mice | Mice, Knockout

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Associated grants

  • Agency: NIDDK NIH HHS, Id: K01 5 K01 DK64924-02
  • Agency: NHLBI NIH HHS, Id: P01 HL32262
  • Agency: NICHD NIH HHS, Id: P30-HD 18655

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