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

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.