H ferritin knockout mice: A model of hyperferritinemia in the absence of iron overload

Chrystophe Ferreira, Paolo Santambrogio, Marie Elise Martin, Valérie Andrieu, Gérard Feldmann, Dominique Hénin, Carole Beaumont

Research output: Contribution to journalArticlepeer-review


Ferritin, the iron-storing molecule, is made by the assembly of various proportions of 2 different H and L subunits into a 24-mer protein shell. These heteropolymers have distinct physicochemical properties, owing to the ferroxidase activity of the H subunit, which is necessary for iron up-take by the ferritin molecule, and the ability of the L subunit to facilitate iron core formation inside the protein shell. It has previously been shown that H ferritin is indispensable for normal development, since inactivation of the H ferritin gene by homologous recombination in mice is lethal at an early stage during embryonic development. Here the phenotypic analysis of the mice heterozygous for the H ferritin gene (Fth+/- mice) is reported, and differences in gene regulation between the 2 subunits are shown. The heterozygous Fth+/- mice were healthy and fertile and did not present any apparent abnormalities. Although they had iron-overloaded spleens at the adult stage, this is identical to what is observed in normal Fth+/+ mice. However, these heterozygous mice had slightly elevated tissue L ferritin content and 7- to 10-fold more L ferritin in the serum than normal mice, but their serum iron remained unchanged. H ferritin synthesis from the remaining allele was not up-regulated. This probably results from subtle changes in the intracellular labile iron pool, which would stimulate L ferritin but not H ferritin synthesis. These results raise the possibility that reduced H ferritin expression might be responsible for unexplained human cases of hyperferritinemia in the absence of iron overload where the hereditary hyperferritinemia-cataract syndrome has been excluded.

Original languageEnglish
Pages (from-to)525-532
Number of pages8
Issue number3
Publication statusPublished - Aug 1 2001

ASJC Scopus subject areas

  • Hematology


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