Molecular analysis of iron overload in beta2-microglobulin-deficient mice.
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.
European Molecular Biology Laboratory, D-69117, Heidelberg, Germany. martina.muckenthaler@med.uni-heidelberg.de
Martina U
MU
Muckenthaler
Pedro
P
Rodrigues
Maria G
MG
Macedo
Belen
B
Minana
Karen
K
Brennan
Elsa M
EM
Cardoso
Matthias W
MW
Hentze
Maria
M
de Sousa
D000818:Animals; D001692:Biological Transport; D015152:Blotting, Northern; D004386:Duodenum / Q000378:metabolism; D006432:Hemochromatosis; D007501:Iron / Q000378:metabolism; D019190:Iron Overload / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D001613:beta 2-Microglobulin / Q000172:deficiency* / Q000235:genetics
D012333:RNA, Messenger; D001613:beta 2-Microglobulin; D007501:Iron