Early embryonic lethality of H ferritin gene deletion in mice

Chrystophe Ferreira, Danièle Bucchini, Marie Elise Martin, Sonia Levi, Paolo Arosio, Bernard Grandchamp, Carole Beaumont

Research output: Contribution to journalArticlepeer-review

Abstract

Ferritin molecules play an important role in the control of intracellular iron distribution and in the constitution of long term iron stores. In vitro studies on recombinant ferritin subunits have shown that the ferroxidase activity associated with the H subunit is necessary for iron uptake by the ferritin molecule, whereas the L subunit facilitates iron core formation inside the protein shell. However, plant and bacterial ferritins have only a single type of subunit which probably fulfills both functions. To assess the biological significance of the ferroxidase activity associated with the H subunit, we disrupted the H ferritin gene (Fth) in mice by homologous recombination. Fth(+/-) mice are healthy, fertile, and do not differ significantly from their control littermates. However, Fth(-/-) embryos die between 3.5 and 9.5 days of development, suggesting that there is no functional redundancy between the two ferritin subunits and that, in the absence of H subunits, L ferritin homopolymers are not able to maintain iron in a bioavailable and nontoxic form. The pattern of expression of the wild type Fth gene in 9.5-day embryos is suggestive of an important function of the H ferritin gene in the heart.

Original languageEnglish
Pages (from-to)3021-3024
Number of pages4
JournalJournal of Biological Chemistry
Volume275
Issue number5
DOIs
Publication statusPublished - Feb 4 2000

ASJC Scopus subject areas

  • Biochemistry

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