Molecular analysis of iron overload in beta2-microglobulin-deficient mice.

• Autor(a) principal: Muckenthaler, Martina U.
• Data de Publicação: 2004
• Outros Autores: Rodrigues, Pedro, Macedo, Maria G., Minana, Belen, Brennan, Karen, Cardoso, Elsa M., Hentze, Matthias W., de Sousa, Maria
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10314/3506; https://doi.org/http://dx.doi.org/10.1016/j.bcmd.2004.05.003
• topic: Hereditary hemochromatosis; Iron metabolism; Hepcidin; DMT-1; Ferroportin 1; Microarray; IronChip; Iron Transporter

Beta2-microglobulin knockout (beta2m-/-) 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 beta2m-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 beta2m-/- mice underlines the importance of hepcidin in regulating body iron stores. In contrast to Hfe-/- mice, beta2m-deficient mice display increased expression of the duodenal iron transporters DMT1 and ferroportin 1. This result implicates a broader role of beta2m in mammalian iron metabolism, suggesting that (an) additional beta2m-interacting protein(s) could be involved in controlling iron homeostasis, and highlighting the emerging connection of iron metabolism with the immune system.