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PMID:15849611

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Citation

Gunshin, H, Fujiwara, Y, Custodio, AO, Direnzo, C, Robine, S and Andrews, NC (2005) Slc11a2 is required for intestinal iron absorption and erythropoiesis but dispensable in placenta and liver. J. Clin. Invest. 115:1258-66

Abstract

Solute carrier family 11, member 2 (SLC11A2) is the only transmembrane iron transporter known to be involved in cellular iron uptake. It is widely expressed and has been postulated to play important roles in intestinal iron absorption, erythroid iron utilization, hepatic iron accumulation, placental iron transfer, and other processes. Previous studies have suggested that other transporters might exist, but their physiological significance remained uncertain. To define the activities of Slc11a2 in vivo, we inactivated the murine gene that encodes it globally and selectively. We found that fetal Slc11a2 is not needed for materno-fetal iron transfer but that Slc11a2 activity is essential for intestinal non-heme iron absorption after birth. Slc11a2 is also required for normal hemoglobin production during the development of erythroid precursors. However, hepatocytes and most other cells must have an alternative, as-yet-unknown, iron uptake mechanism. We previously showed that Slc11a2 serves as the primary portal for intestinal iron entry in hemochromatosis. However, inactivation of murine Hfe ameliorates the phenotype of animals lacking Slc11a2.

Links

PubMed PMC1077176 Online version:10.1172/JCI24356

Keywords

Animals; Cation Transport Proteins/genetics; Cation Transport Proteins/metabolism; Erythropoiesis/physiology; Female; Genes, Reporter; Heterozygote; Homozygote; Integrases; Intestine, Small/metabolism; Iron/metabolism; Iron-Binding Proteins/genetics; Iron-Binding Proteins/metabolism; Liver/metabolism; Mice; Mice, Transgenic; Placenta/metabolism; Pregnancy; Promoter Regions, Genetic

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:NRAM2

acts_upstream_of_or_within

GO:0048821: erythrocyte development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:3577914

P

Seeded From UniProt

complete


See also

References

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