Long-term sequelae of HFE deletion in C57BL/6 × 129/O1a mice, an animal model for hereditary haemochromatosis

A. Lebeau, J. Frank, H. K. Biesalski, G. Weiss, S. K.S. Srai, R. J. Simpson, A. T. McKie, S. Bahram, S. Gilfillan, Klaus Schümann

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Abstract

Background: HFE knockout mice (C57BL/6 × 129/O1a strain) mimic the functional aberrations of human hereditary haemochromatosis (HH) in short-term experiments. The present study investigates functional and morphological long-term changes. Methods: HFE0/0, HFE+/0 and HFE+/+ mice were maintained on iron-rich and control diets for 2 weeks, 3, 12 and 18 months. Light microscopic tissue iron distribution, pathomorphological alterations, tissue iron content and oxidative stress were analysed in liver, pancreas, spleen, gastrointestinal tract, kidneys and myocardium. Additionally, duodenal 59Fe absorption and 59Fe whole body loss were measured. Results: Iron distribution between organs and microscopic iron deposition in the tissues resembled the patterns described in HH. After 3 months of iron-rich feeding duodenal 59Fe absorption decreased to ∼15% of iron-adequate controls but remained about twice as high in HFE0/0 as in HFE+/+ mice. Hepatic iron concentrations reached only half the values known to induce hepatic fibrosis in rats and humans, while whole body 59Fe loss was about twice as high. Consequently no hepatic fibrosis developed, although massive hepatocellular iron deposition and indication for oxidative stress were observed. Conclusion: C57BL/6 × 129/O1a HFE0/0 mice mimic HH iron distribution and the regulation of intestinal iron absorption after long-term feeding. However, characteristic morphological late changes in untreated HH are not modelled.

Original languageEnglish
Pages (from-to)603-612
Number of pages10
JournalEuropean Journal of Clinical Investigation
Volume32
Issue number8
DOIs
StatePublished - Dec 1 2002

Keywords

  • Absorption
  • HFE knockout
  • Haemochromatosis
  • Hepatic fibrosis
  • Iron
  • Loss

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    Lebeau, A., Frank, J., Biesalski, H. K., Weiss, G., Srai, S. K. S., Simpson, R. J., McKie, A. T., Bahram, S., Gilfillan, S., & Schümann, K. (2002). Long-term sequelae of HFE deletion in C57BL/6 × 129/O1a mice, an animal model for hereditary haemochromatosis. European Journal of Clinical Investigation, 32(8), 603-612. https://doi.org/10.1046/j.1365-2362.2002.01026.x