Previously, hepatic iron overload resembling that in hereditary hemachromatosis (HH) has been found in beta 2-microglobulin knockout (beta 2m-/-) mice. We have now characterized iron metabolism in beta 2m-/- mice. The mutant mice fail to limit the transfer of iron from mucosal cells into the plasma. Transferrin saturation is abnormally high. Pathologic iron depositions occur predominantly in liver parenchymal cells. Reconstitution with normal hematopoietic cells redistributes the iron from parenchymal to Kupffer cells, but does not correct the mucosal defect. We conclude that (a) iron metabolism is defective in the gut mucosa as well as the liver of beta 2m-/- mice; and (b) a beta 2m-dependent gene product is involved in iron homeostasis. Recently, a novel gene of the major histocompatibility complex class I family, HLA-H, has been found to be mutated in a large proportion of HH patients. Our data provide functional support for the proposed causative role of HLA-H mutations in HH.
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November 01 1996
Defective iron homeostasis in beta 2-microglobulin knockout mice recapitulates hereditary hemochromatosis in man.
M Santos,
M Santos
Department of Immunology, Eijkman-Winkler Institute, Utrecht, The Netherlands.
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M W Schilham,
M W Schilham
Department of Immunology, Eijkman-Winkler Institute, Utrecht, The Netherlands.
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L H Rademakers,
L H Rademakers
Department of Immunology, Eijkman-Winkler Institute, Utrecht, The Netherlands.
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J J Marx,
J J Marx
Department of Immunology, Eijkman-Winkler Institute, Utrecht, The Netherlands.
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M de Sousa,
M de Sousa
Department of Immunology, Eijkman-Winkler Institute, Utrecht, The Netherlands.
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H Clevers
H Clevers
Department of Immunology, Eijkman-Winkler Institute, Utrecht, The Netherlands.
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M Santos
Department of Immunology, Eijkman-Winkler Institute, Utrecht, The Netherlands.
M W Schilham
Department of Immunology, Eijkman-Winkler Institute, Utrecht, The Netherlands.
L H Rademakers
Department of Immunology, Eijkman-Winkler Institute, Utrecht, The Netherlands.
J J Marx
Department of Immunology, Eijkman-Winkler Institute, Utrecht, The Netherlands.
M de Sousa
Department of Immunology, Eijkman-Winkler Institute, Utrecht, The Netherlands.
H Clevers
Department of Immunology, Eijkman-Winkler Institute, Utrecht, The Netherlands.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1996) 184 (5): 1975–1985.
Citation
M Santos, M W Schilham, L H Rademakers, J J Marx, M de Sousa, H Clevers; Defective iron homeostasis in beta 2-microglobulin knockout mice recapitulates hereditary hemochromatosis in man.. J Exp Med 1 November 1996; 184 (5): 1975–1985. doi: https://doi.org/10.1084/jem.184.5.1975
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