Comparative analysis of mouse hepcidin 1 and 2 genes: evidence for different patterns of expression and co-inducibility during iron overload.
In contrast to the human genome, the mouse genome contains two HEPC genes encoding hepcidin, a key regulator of iron homeostasis. Here we report a comparative analysis of sequence, genomic structure, expression and iron regulation of mouse HEPC genes. The predicted processed 25 amino acid hepcidin 2 peptide share 68% identity with hepcidin 1 with perfect conservation of eight cysteine residues. Both HEPC1 and HEPC2 genes have similar genomic organization and have probably arisen from a recent duplication of chromosome 7 region, including the HEPC ancestral gene and a part of the adjacent USF2 gene. Insertion of a retroviral intracisternal A-particle element was found upstream of the HEPC1 gene. Both genes are highly expressed in the liver and to a much lesser extent in the heart. In contrast to HEPC1, a high amount of HEPC2 transcripts was detected in the pancreas. Expression of both genes was increased in the liver during carbonyl-iron and iron-dextran overload. Overall our data suggest that both HEPC1 and HEPC2 genes are involved in iron metabolism regulation but could exhibit different activities and/or play distinct roles.
Ilyin
Gennady
G
INSERM U522, Hôpital Pontchaillou, 35033 Rennes, France. guennadi.iline@rennes.inserm.fr
Courselaud
Brice
B
Troadec
Marie Bérengère
MB
Pigeon
Christelle
C
Alizadeh
Mehdi
M
Leroyer
Patricia
P
Brissot
Pierre
P
Loréal
Olivier
O
D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis / Q000235:genetics*; D001483:Base Sequence; D040461:Gene Components; D005786:Gene Expression Regulation; D064451:Hepcidins; D019190:Iron Overload / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis; D014018:Tissue Distribution
D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; C579599:Hamp protein, mouse; C474320:Hamp2 protein, mouse; D064451:Hepcidins; D012333:RNA, Messenger