| First Author | Ferreira C | Year | 2001 |
| Journal | Blood | Volume | 98 |
| Issue | 3 | Pages | 525-32 |
| PubMed ID | 11468145 | Mgi Jnum | J:70685 |
| Mgi Id | MGI:2138002 | Doi | 10.1182/blood.v98.3.525 |
| Citation | Ferreira C, et al. (2001) H ferritin knockout mice: a model of hyperferritinemia in the absence of iron overload. Blood 98(3):525-32 |
| abstractText | 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 uptake 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. (Blood. 2001;98:525-532) |
