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 hepcidin genes, hepc1 and hepc2, 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 overexpressing hepc1 in the liver. Here we report that, in contrast to the hepc1-transgenic mice, none of the 7 founder hepc2-transgenic animals suffered from anemia. They all developed normally with hematologic parameters similar to the nontransgenic littermates. Hepc2 transgenic mRNA level was found to be very high for all lines compared with the level of hepc1 transgene 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.
Lou
Dan-Qing
DQ
Département de Génétique, Développement et Pathologie Moléculaire, Institut Cochin, Faculté de Médecine Cochin-Port Royal, Paris, France.
Nicolas
Gaël
G
Lesbordes
Jeanne-Claire
JC
Viatte
Lydie
L
Grimber
Gisèle
G
Szajnert
Marie-France
MF
Kahn
Axel
A
Vaulont
Sophie
S
D000595:Amino Acid Sequence; D000740:Anemia / Q000235:genetics*; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics*; D001483:Base Sequence; D017931:DNA Primers; D018703:Founder Effect; D016678:Genome; D006402:Hematologic Diseases / Q000235:genetics; D064451:Hepcidins; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013552:Swine
D023181:Antimicrobial Cationic Peptides; D017931:DNA Primers; C578702:HAMP protein, human; C579599:Hamp protein, mouse; C578703:Hamp protein, rat; C474320:Hamp2 protein, mouse; D064451:Hepcidins; D012333:RNA, Messenger; D012313:RNA