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Mislocalisation of hephaestin, a multicopper ferroxidase involved in basolateral intestinal iron transport, in the sex linked anaemia mouse
  1. Y M Kuo1,
  2. T Su2,
  3. H Chen2,
  4. Z Attieh2,
  5. B A Syed3,
  6. A T McKie4,
  7. G J Anderson5,
  8. J Gitschier1,
  9. C D Vulpe2
  1. 1Departments of Medicine and Pediatrics and Howard Hughes Medical Institute, University of California, San Francisco, CA 94143-0794, USA
  2. 2Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720-3104, USA
  3. 3Metalloprotein Research Group, The Randall Centre, New Hunts House, Kings College London, SE1 9RT, UK
  4. 4Department of Molecular Medicine, King’s College, London SE5 9NU, UK
  5. 5Queensland Institute of Medical Research and the University of Queensland, Post Office Royal Brisbane Hospital, Brisbane, Queensland 4029, Australia
  1. Correspondence to:
    Assistant Professor C D Vulpe
    Department of Nutrition and Toxicology, University of California, Berkeley, 119 Morgan Hall, Berkeley, CA 94720, USA; vulpeuclink4.berkeley.edu

Abstract

Background: Hephaestin is a multicopper ferroxidase required for basolateral transport of iron from enterocytes. Sex linked anaemia (sla) mice have a defect in the release of iron from intestinal enterocytes into the circulation due to an interstitial deletion in the hephaestin gene (heph).

Results: We have demonstrated that hephaestin is primarily localised to a supranuclear compartment in both intestinal enterocytes and in cultured cells. In normal intestinal enterocytes, hephaestin was also present on the basolateral surface. In sla mice, hephaestin was present only in the supranuclear compartment. In contrast, the iron permease Ireg1 localised to the basolateral membrane in both control and sla mice.

Conclusion: We suggest that mislocalisation of hephaestin likely contributes to the functional defect in sla intestinal epithelium.

  • iron
  • intestine
  • sex linked anaemia
  • anaemia
  • haemochromatosis
  • Hp, hephaestin
  • Cp, ceruloplasmin
  • sla, sex linked anaemia
  • Tfr, transferrin receptor
  • DAB, 3,3′-diaminobenzidine

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