Conditional Deletion of Ferritin H in Mice Induces Loss of Iron Storage and Liver Damage

Darshan, Deepak, Vanoaica, Liviu, Richman, Larry, Beermann, Friedrich and Kuehn, Lukas C. (2009) Conditional Deletion of Ferritin H in Mice Induces Loss of Iron Storage and Liver Damage. Hepatology, 50 3: 852-860. doi:10.1002/hep.23058


Author Darshan, Deepak
Vanoaica, Liviu
Richman, Larry
Beermann, Friedrich
Kuehn, Lukas C.
Title Conditional Deletion of Ferritin H in Mice Induces Loss of Iron Storage and Liver Damage
Journal name Hepatology   Check publisher's open access policy
ISSN 0270-9139
1527-3350
Publication date 2009-09-01
Year available 2009
Sub-type Article (original research)
DOI 10.1002/hep.23058
Open Access Status Not yet assessed
Volume 50
Issue 3
Start page 852
End page 860
Total pages 9
Place of publication Hoboken, NJ United States
Publisher John Wiley and Sons Inc
Language eng
Formatted abstract
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. 
Keyword Antimicrobial Peptide Hepcidin
Erythroleukemia Cells
Hemoglobin Synthesis
Oxidative Stress
Messenger Rna
Hemochromatosis
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID KFS 1000-02-2000
3100-065435
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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