Functional differences between hepcidin 1 and 2 in transgenic mice

Hepcidin is a 25-amino acid peptide involved in iron homeostasis in mice and humans. It is produced in the liver from a larger precursor, and it is detectable in blood and urine. In contrast to the human genome, which contains only one copy of the gene, the mouse genome contains 2 highly similar hep...

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Bibliographic Details
Published in:Blood 2004-04, Vol.103 (7), p.2816-2821
Main Authors: Lou, Dan-Qing, Nicolas, Gaël, Lesbordes, Jeanne-Claire, Viatte, Lydie, Grimber, Gisèle, Szajnert, Marie-France, Kahn, Axel, Vaulont, Sophie
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Anemia - genetics
Anemias. Hemoglobinopathies
Animals
Antimicrobial Cationic Peptides - genetics
Base Sequence
Biological and medical sciences
Diseases of red blood cells
DNA Primers
Founder Effect
Genome
Hematologic and hematopoietic diseases
Hematologic Diseases - genetics
Hepcidins
Humans
Medical sciences
Mice
Mice, Inbred C57BL
Mice, Transgenic
Molecular Sequence Data
Rats
RNA - genetics
RNA - isolation & purification
RNA, Messenger - genetics
Sequence Alignment
Sequence Homology, Amino Acid
Swine
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Summary:Hepcidin is a 25-amino acid peptide involved in iron homeostasis in mice and humans. It is produced in the liver from a larger precursor, and it is detectable in blood and urine. In contrast to the human genome, which contains only one copy of the gene, the mouse genome contains 2 highly similar hepcidin genes,hepc1andhepc2, which are, however, considerably divergent at the level of the corresponding mature 25-amino acid peptide. This striking observation led us to ask whether hepc1 and hepc2 performed the same biologic activity with regard to iron metabolism in the mouse. We recently described the severe iron-deficient anemia phenotype in transgenic mice overexpressinghepc1in the liver. Here we report that, in contrast to thehepc1-transgenic mice, none of the 7 founderhepc2-transgenic animals suffered from anemia. They all developed normally with hematologic parameters similar to the nontransgenic littermates. Hepc2transgenic mRNA level was found to be very high for all lines compared with the level ofhepc1transgene mRNA necessary to produce severe anemia. These data provide evidence that hepc2 does not act on iron metabolism like hepc1 and give clues for the identification of amino acids important for the iron-regulatory action of the mature 25-amino acid peptide. (Blood. 2004;103:2816-2821)
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2003-07-2524