Document Detail


Functional differences between hepcidin 1 and 2 in transgenic mice.
MedLine Citation:
PMID:  14604961     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Dan-Qing Lou; Gaël Nicolas; Jeanne-Claire Lesbordes; Lydie Viatte; Gisèle Grimber; Marie-France Szajnert; Axel Kahn; Sophie Vaulont
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2003-11-06
Journal Detail:
Title:  Blood     Volume:  103     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  2004 Apr 
Date Detail:
Created Date:  2004-03-22     Completed Date:  2004-05-11     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2816-21     Citation Subset:  AIM; IM    
Affiliation:
Département de Génétique, Développement et Pathologie Moléculaire, Institut Cochin, Faculté de Médecine Cochin-Port Royal, Paris, France.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Anemia / genetics*
Animals
Antimicrobial Cationic Peptides / genetics*
Base Sequence
DNA Primers
Founder Effect
Genome
Hematologic Diseases / genetics
Humans
Mice
Mice, Inbred C57BL
Mice, Transgenic
Molecular Sequence Data
RNA / genetics,  isolation & purification
RNA, Messenger / genetics
Rats
Sequence Alignment
Sequence Homology, Amino Acid
Swine
Chemical
Reg. No./Substance:
0/Antimicrobial Cationic Peptides; 0/DNA Primers; 0/Hamp2 protein, mouse; 0/RNA, Messenger; 0/hepcidin; 63231-63-0/RNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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