Document Detail


Hepcidin antimicrobial peptide transgenic mice exhibit features of the anemia of inflammation.
MedLine Citation:
PMID:  17218383     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The anemia of inflammation is an acquired disorder affecting patients with a variety of medical conditions, and it is characterized by changes in iron homeostasis and erythropoiesis. Mounting evidence suggests that hepcidin antimicrobial peptide plays a primary role in the pathogenesis of the anemia of inflammation. To evaluate which features of this anemia can be attributed to hepcidin, we have generated mice carrying a tetracycline-regulated hepcidin transgene. Expression of the hepcidin transgene resulted in down-regulation of endogenous hepcidin mRNA. The transgenic mice developed a mild-to-moderate anemia associated with iron deficiency and iron-restricted erythropoiesis. Similar to the anemia of inflammation, iron accumulated in tissue macrophages, whereas a relative paucity of iron was found in the liver. Circulating erythrocytes in transgenic animals had normal survival rates, but transgenic animals had an impaired response to erythropoietin. Thus, hepcidin transgenic mice recapitulate each of the key features of anemia of inflammation in human patients and serve as a useful model of this prevalent disorder.
Authors:
Cindy N Roy; Howard H Mak; Imo Akpan; Grigoriy Losyev; David Zurakowski; Nancy C Andrews
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-01-11
Journal Detail:
Title:  Blood     Volume:  109     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  2007 May 
Date Detail:
Created Date:  2007-04-23     Completed Date:  2007-06-05     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4038-44     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Anemia, Iron-Deficiency / genetics,  metabolism*,  pathology
Animals
Antimicrobial Cationic Peptides / biosynthesis*,  genetics
Cell Survival / genetics
Disease Models, Animal
Erythrocytes / metabolism,  pathology
Erythropoiesis* / drug effects,  genetics
Erythropoietin / pharmacology
Hepcidins
Inflammation / genetics,  metabolism,  pathology
Iron / metabolism
Macrophages / metabolism,  pathology
Mice
Mice, Transgenic
Grant Support
ID/Acronym/Agency:
K01 DK 065635/DK/NIDDK NIH HHS; K01 DK065635/DK/NIDDK NIH HHS; K01 DK065635-04/DK/NIDDK NIH HHS; R01 DK 053813/DK/NIDDK NIH HHS; R01 DK053813/DK/NIDDK NIH HHS; R01 DK053813-10/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Antimicrobial Cationic Peptides; 0/HAMP protein, human; 0/Hamp1 protein, mouse; 0/Hepcidins; 11096-26-7/Erythropoietin; E1UOL152H7/Iron
Comments/Corrections

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