|
|
 Previous Article | Table of Contents | Next Article 
Adaptive Response of Iron Absorption to Anemia, Increased
Erythropoiesis, Iron Deficiency, and Iron Loading in
 2-Microglobulin Knockout Mice
Manuela Santos,
Hans Clevers,
Maria de Sousa, and
J.J.M. Marx
From the Departments of Immunology and Internal Medicine and
Eijkman-Winkler Institute, University Hospital Utrecht, Utrecht, The
Netherlands; and Molecular Pathology and Immunology, Abel Salazar
Institute for the Biomedical Sciences, Porto, Portugal.
Recently, a novel gene of the major histocompatibility complex (MHC)
class I family, HFE (HLA-H), has been found to be mutated in a large
proportion of hereditary hemochromatosis (HH) patients. Further support
for a causative role of HFE in this disease comes from the observation
that  2-microglobulin knockout (2m /) mice, that
fail to express MHC class I products, develop iron overload. We have
now used this animal model of HH to examine the capacity to adapt iron
absorption in response to altered iron metabolism in the absence of
2m-dependent molecule(s). Mucosal uptake, mucosal transfer and
retention of iron were measured in control and 2m/
mice with altered iron metabolism. Mucosal uptake of Fe(III), but not
of Fe(II), by the mutant mice was significantly higher when compared
with B6 control mice. Mucosal transfer in the 2m/
mice was higher, independent of the iron form tested. No significant differences were found in iron absorption between control and 2m/ mice when anemia was induced either by
repetitive bleeding or by hemolysis through phenylhydrazine treatment.
However, iron absorption in mice made anemic by dietary deprivation of
iron was significantly higher in the mutant mice. Furthermore, the 2m/ mice manifested an impaired capacity to
downmodulate iron absorption when dietary or parenterally iron-loaded.
The expression of the defect in iron absorption in the
2m/ mice is quantitative, with iron absorption
being excessively high for the size of body iron stores. The higher
iron absorption capacity in the 2m/ mice may
involve the initial step of ferric mucosal uptake and the subsequent
step of mucosal transfer of iron to the plasma.
Blood, Vol. 91 No. 8 (April 15), 1998:
pp. 3059-3065
© 1998 by The American Society of Hematology.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
M. Constante, W. Jiang, D. Wang, V.-A. Raymond, M. Bilodeau, and M. M. Santos
Distinct requirements for Hfe in basal and induced hepcidin levels in iron overload and inflammation
Am J Physiol Gastrointest Liver Physiol,
August 1, 2006;
291(2):
G229 - G237.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Makui, R. J. Soares, W. Jiang, M. Constante, and M. M. Santos
Contribution of Hfe expression in macrophages to the regulation of hepatic hepcidin levels and iron loading
Blood,
September 15, 2005;
106(6):
2189 - 2195.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. J. P. Gobin, P. Biesta, and P. J. Van den Elsen
Regulation of human beta 2-microglobulin transactivation in hematopoietic cells
Blood,
April 15, 2003;
101(8):
3058 - 3064.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. J. Simpson, E. S. Debnam, A. H. Laftah, N. Solanky, N. Beaumont, S. Bahram, K. Schumann, and S. K. S. Srai
Duodenal nonheme iron content correlates with iron stores in mice, but the relationship is altered by Hfe gene knock-out
Blood,
April 15, 2003;
101(8):
3316 - 3318.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Tolosano, S. Fagoonee, E. Hirsch, F. G. Berger, H. Baumann, L. Silengo, and F. Altruda
Enhanced splenomegaly and severe liver inflammation in haptoglobin/hemopexin double-null mice after acute hemolysis
Blood,
December 1, 2002;
100(12):
4201 - 4208.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Moos, D. Trinder, and E. H. Morgan
Effect of iron status on DMT1 expression in duodenal enterocytes from beta 2-microglobulin knockout mice
Am J Physiol Gastrointest Liver Physiol,
September 1, 2002;
283(3):
G687 - G694.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Canonne-Hergaux, J. E. Levy, M. D. Fleming, L. K. Montross, N. C. Andrews, and P. Gros
Expression of the DMT1 (NRAMP2/DCT1) iron transporter in mice with genetic iron overload disorders
Blood,
February 15, 2001;
97(4):
1138 - 1140.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. N. Roy and C. A. Enns
Iron homeostasis: new tales from the crypt
Blood,
December 15, 2000;
96(13):
4020 - 4027.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. M. Santos, M. de Sousa, L. H. P. M. Rademakers, H. Clevers, J. J. M. Marx, and M. W. Schilham
Iron Overload and Heart Fibrosis in Mice Deficient for Both {beta}2-Microglobulin and Rag1
Am. J. Pathol.,
December 1, 2000;
157(6):
1883 - 1892.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. O. Sousa, R. J. Mazzaccaro, R. G. Russell, F. K. Lee, O. C. Turner, S. Hong, L. Van Kaer, and B. R. Bloom
Relative contributions of distinct MHC class I-dependent cell populations in protection to tuberculosis infection in mice
PNAS,
April 11, 2000;
97(8):
4204 - 4208.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Canonne-Hergaux, S. Gruenheid, P. Ponka, and P. Gros
Cellular and Subcellular Localization of the Nramp2 Iron Transporter in the Intestinal Brush Border and Regulation by Dietary Iron
Blood,
June 15, 1999;
93(12):
4406 - 4417.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Yu, Z. K. Yu, and M. Wessling-Resnick
Expression of SFT (Stimulator of Fe Transport) Is Enhanced by Iron Chelation in HeLa Cells and by Hemochromatosis in Liver
J. Biol. Chem.,
December 25, 1998;
273(52):
34675 - 34678.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Pigeon, G. Ilyin, B. Courselaud, P. Leroyer, B. Turlin, P. Brissot, and O. Loreal
A New Mouse Liver-specific Gene, Encoding a Protein Homologous to Human Antimicrobial Peptide Hepcidin, Is Overexpressed during Iron Overload
J. Biol. Chem.,
March 9, 2001;
276(11):
7811 - 7819.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
