These authors contributed equally to this work.
Conditional deletion of ferritin H in mice induces loss of iron storage and liver damage†
Article first published online: 6 MAY 2009
Copyright © 2009 American Association for the Study of Liver Diseases
Volume 50, Issue 3, pages 852–860, September 2009
How to Cite
Darshan, D., Vanoaica, L., Richman, L., Beermann, F. and Kühn, L. C. (2009), Conditional deletion of ferritin H in mice induces loss of iron storage and liver damage. Hepatology, 50: 852–860. doi: 10.1002/hep.23058
Potential conflict of interest: Nothing to report.
- Issue published online: 27 AUG 2009
- Article first published online: 6 MAY 2009
- Accepted manuscript online: 6 MAY 2009 12:00AM EST
- Manuscript Accepted: 28 APR 2009
- Manuscript Received: 27 FEB 2009
- Swiss Cancer League. Grant Number: KFS 1000-02-2000
- Swiss National Science Foundation. Grant Number: 3100-065435
Ferritin plays a central role in iron metabolism by acting both as iron storage and a detoxifying protein. We generated a ferritin H allele with loxP sites and studied the conditional ferritin H deletion in adult mice. Ten days after Mx-Cre induced deletion, ferritin H messenger RNA (mRNA) was below 5% in the liver, spleen, and bone marrow of deleted mice compared to control littermates. Mice lost their cellular iron stores indicating the requirement of ferritin H in iron deposition. Serum iron and transferrin saturation were slightly increased and correlated with a two-fold increased liver hepcidin 1 mRNA and a reduced duodenal DcytB mRNA level. Under a normal iron regimen, deleted mice survived for 2 years without visible disadvantage. Mice fed on a high iron diet prior to ferritin H deletion suffered from severe liver damage. Similarly, ferritin H deleted mouse embryonic fibroblasts showed rapid cell death after exposure to iron salt in the medium. This was reversed by wild-type ferritin H but not by a ferritin H mutant lacking ferroxidase activity. Cell death was preceded by an increase in cytoplasmic free iron, reactive oxygen species, and mitochondrial depolarization. Conclusion: Our results provide evidence that the iron storage function of ferritin plays a major role in preventing iron-mediated cell and tissue damage. (HEPATOLOGY 2009.)