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Targeted disruption of the hepcidin 1 gene results in severe hemochromatosis
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We previously reported that mice made deficient for the transcriptional factor USF2 fail to express hepcidin 1 and hepcidin 2 genes as a consequence of targeted disruption of the Usf2 gene lying just upstream in the locus. These mice developed an iron overload phenotype with excess iron deposition in parenchymal cells and decreased reticuloendothelial iron. At that time, although the role of USF2 was still confounding, we proposed for the first time the role of hepcidin as a negative regulator of iron absorption and iron release from macrophages. Accordingly, we subsequently demonstrated that hyperexpression of hepcidin 1, but not hepcidin 2, resulted in a profound hyposideremic anemia. To analyze the consequences of hepcidin 1 deletion on iron metabolism without any disturbance due to USF2 deficiency, we disrupted the hepcidin 1 gene by targeting almost all the coding region. Confirming our prior results, Hepc1–/– mice developed early and severe multivisceral iron overload, with sparing of the spleen macrophages, and demonstrated increased serum iron and ferritin levels as compared with their controls.
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“The functional effects of altered hepcidin expression in vivo were apparent when Nicolas, Lesbordes-Brion, and colleagues showed that inactivation of the hepcidin gene in mice was associated with severe iron overload.101,102”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [102]
In the citing paper
“that acts in part as a negative regulator of iron efflux [328] by causing the internalisation of ferroportin [329-333].”
In the citing paper
“As previously described (14), Hamp−/− mice present a higher hematocrit (60%) and a higher concentration of iron and ferritin in the blood when compared to WT (Figures 3A–C).”
From Iron- and Hepcidin-Independent Downregulation of the Iron Exporter Ferroportin in Macrophages during Salmonella Infection (2017) · cites this paper as [14]
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“Hamp−/− mice have been shown to develop a specific iron phenotype with high serum iron concentration, excess iron deposition in hepatocytes, and low iron levels in tissue macrophages (14).”
From Iron- and Hepcidin-Independent Downregulation of the Iron Exporter Ferroportin in Macrophages during Salmonella Infection (2017) · cites this paper as [14]
In the citing paper
“The suppression of hepcidin alone cannot fully explain the polycythemia associated with testosterone administration because hemochromatosis patients with inactivating mutations in the hepcidin gene (hAMP) and mice with disruption of the hepcidin gene expression do not display a phenotype of polycythemia (27,28).”
From Testosterone induces erythrocytosis via increased erythropoietin and suppressed hepcidin: evidence for a new erythropoietin/hemoglobin set point (2014) · cites this paper as [27]
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Metadata
- Authors
- Lesbordes-Brion, J.-C., Viatte, L., Bennoun, M., Lou, D.-Q., Ramey, G., Houbron, C., Hamard, G., Kahn, A., & Vaulont, S.
- Affiliations
- From the Institut Cochin, Département de Génétique, Développement et Pathologie Moléculaire; Institut National de la Santé et de la Recherche Médicale (INSERM) U567; Centre National de la Recherche Scientifique (CNRS); and Université Paris Descartes, Faculté de Médecine René Descartes, Paris, France.
- Centre National de la Recherche Scientifique (FR)
- ORCID
- Vaulont, Sophie
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2006-08-15
- Volume
- 108
- Issue
- 4
- Pages
- 1402-1405
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W1987067683
- Cited by
- 257
- References
- 23
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 8 · 2023: 4 · 2022: 9 · 2021: 9 · 2020: 19 · 2019: 13 · 2018: 8 · 2017: 21 · 2016: 16 · 2015: 16 · 2014: 21 · 2013: 19 · 2012: 13
- FWCI
- 7.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
- Keywords
- hemochromatosis, iron overload, iron metabolism, knockout mice, USF2, serum iron, ferritin, splenic macrophages
- MeSH terms
- Animals, Ferritins, Hemochromatosis, Iron, Macrophages, Spleen, Open Reading Frames, Gene Deletion, Mice, Knockout, Antimicrobial Cationic Peptides, Quantitative Trait Loci, Mice, Upstream Stimulatory Factors, Hepcidins
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