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Prepublished online as a Blood First Edition Paper on December 5, 2002; DOI 10.1182/blood-2002-10-3112.

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Submitted October 15, 2002
Accepted November 22, 2002

Duodenal non-heme iron content correlates with iron stores in mice, but the relationship is altered by Hfe gene knock-out

Robert J Simpson*, Edward S Debnam, Abas H Laftah, Nita Solanky, Nicholas Beamont, Seiamak Bahram, Klaus Schumann, and Surjit K Srai

Life Sciences, Kings College London, London, United Kingdom
Physiology, Royal Free and University College School of Medicine, London, United Kingdom
Molecular Biology, Royal Free and University College School of Medicine, London, United Kingdom
INSERM-CreS, Centre de Recherche dImmunologie et dHematologie, Strasbourg, France
Walther-Straub-Institut fur Pharmakologie und Toxikologie, Ludwig-Maximilians-Universitat, Munchen, Germany

* Corresponding author; email: robert.simpson{at}kcl.ac.uk.

Rationale: Hereditary hemochromatosis is a common iron-loading disorder found in populations of European descent. It has been proposed that mutations causing loss of function of HFE gene result in reduced iron incorporation into immature duodenal crypt cells. These cells then over-express genes for iron absorption leading to inappropriate cellular iron balance, a persistent iron deficiency of the duodenal mucosa and increased iron absorption. Objective: To measure duodenal iron content in Hfe knockout mice to test whether the mutation causes a persistent decrease in enterocyte iron concentration. Findings: In both normal and Hfe knock-out mice, duodenal non-heme iron content was found to correlate with liver iron stores (p<0.001, r=0.643 and 0.551, respectively) and this effect did not depend on dietary iron levels. However, duodenal iron content was reduced in Hfe knock-out mice for any given content of liver iron stores (p<0.001).


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