Transgenic Res. 2015 Apr 23. [Epub ahead of print]
Lu, S; Seravalli, J; Harrison-Findik, D
University of Nebraska Medical Center, Omaha, NE, USA.
Hepcidin, a circulatory antimicrobial peptide, is involved in iron homeostasis, inflammation, infection and metabolic signals. Humans express one hepcidin gene, HAMP but mice express two hepcidin genes, Hamp1 and Hamp2. Consecutive gene targeting events were performed to produce transgenic mice expressing conditional alleles of either Hamp1 or both Hamp1 and Hamp2 (Hamp1/2). The deletion of Hamp1 alleles elevated Hamp2 expression, particularly in males, which was reduced by endotoxin treatment. The tissue levels of iron and other biometals were quantified by inductively coupled mass spectrometry. The ubiquitous or liver-specific deletion of Hamp1 alleles yielded similar quantitative changes in iron levels in the liver, duodenum, spleen, kidney, heart and brain. The introduction of Hamp2 null allele did not exacerbate the iron-related phenotype of Hamp1 null allele. Besides iron, Hamp1 null allele significantly elevated the levels of selenium in the liver, manganese in the liver and duodenum, and copper in the brain. Mice with conditional Hamp alleles will be useful to determine the tissue-specific regulation and functions of Hamp1 and Hamp2 in biometal homeostasis and other biological processes.
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