Molecular analysis of iron overload in β2-microglobulin-deficient mice

• Published in: Blood cells, molecules, & diseases Vol. 33; no. 2; pp. 125 - 131
• Main Authors: Muckenthaler, Martina U, Rodrigues, Pedro, Macedo, Maria G, Minana, Belen, Brennan, Karen, Cardoso, Elsa M, Hentze, Matthias W, de Sousa, Maria
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.09.2004
• Subjects: DMT-1; Ferroportin 1; Hepcidin; Hereditary hemochromatosis; Iron metabolism; Iron transporter; IronChip; Microarray; Hereditary hemochromatosis; IronChip; Iron metabolism; Ferroportin 1; Iron transporter; Microarray; Hepcidin; DMT-1
• ISSN: 1079-9796; 1096-0961
• DOI: 10.1016/j.bcmd.2004.05.003

β2-microglobulin knockout ( β2m−/−) mice represent an instructive model of spontaneous iron overload resembling genetic hemochromatosis. The mechanism of iron accumulation in this mouse model may be more complex than involving the MHC class I-like protein HFE. We report that β2m-deficient mice, like Hfe−/− mice, lack the adaptive hepatic hepcidin mRNA increase to iron overload. The inverse correlation of hepatic iron levels and hepcidin mRNA expression in six β2m−/− mice underlines the importance of hepcidin in regulating body iron stores. In contrast to Hfe−/− mice, β2m-deficient mice display increased expression of the duodenal iron transporters DMT1 and ferroportin 1. This result implicates a broader role of β2m in mammalian iron metabolism, suggesting that (an) additional β2m-interacting protein(s) could be involved in controlling iron homeostasis, and highlighting the emerging connection of iron metabolism with the immune system.