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Slc11a2 is required for intestinal iron absorption and erythropoiesis but dispensable in placenta and liver
Open accessAbstract
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.
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“However, inorganic iron uptake from the gastrointestinal lumen by enterocytes depends upon the divalent metal transporter protein 1 (DMT1 or NRAMP2), which is not able to import Fe3+. 12 , 13 , 14”
From The battle for iron in enteric infections (2020) · cites this paper as [13]
In the citing paper
“Mammals acquire ferrous (Fe2+) from the diet via a mechanism assisted by the divalent metal transporter ion transporter 1 (DMT1) expressed by duodenum enterocytes (12, 13).”
From Innate Nutritional Immunity (2018) · cites this paper as [12]
In the citing paper
“Surprisingly, however, most other cell types do not appear to require DMT1 for iron uptake.”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [66]
In the citing paper
“Targeted disruption of the murine gene encoding DMT1 confirmed that DMT1 is the primary transmembrane iron transporter bringing dietary nonheme iron into intestinal epithelial cells and mediating iron uptake through the transferrin cycle in erythroid precursors.66”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [66]
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Metadata
- Authors
- Gunshin, H., Fujiwara, Y., Custodio, A. O., DiRenzo, C., Robine, S., & Andrews, N. C.
- Affiliations
- Boston Children's Hospital (US)
- Institut Curie (FR)
- Corresponding author
- Andrews, Nancy C.
- Venue
- Journal of Clinical Investigation
- Published
- 2005-04-21
- Volume
- 115
- Issue
- 5
- Pages
- 1258-1266
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2135216513
- Cited by
- 419
- References
- 38
- Citations by year
- 2026: 9 · 2025: 18 · 2024: 16 · 2023: 20 · 2022: 21 · 2021: 15 · 2020: 14 · 2019: 17 · 2018: 19 · 2017: 17 · 2016: 17 · 2015: 12 · 2014: 25 · 2013: 33 · 2012: 23
- FWCI
- 14.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- American Gastroenterological Association
- National Institutes of Health (5k01dk002804-03)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK049216, R01 DK53813, K01 DK02804, P30 DK49216, R01DK053813)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD018655, P30HD-18655)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- DMT1, ferroportin, intestinal iron absorption, erythropoiesis, placental iron transfer, hepatic iron deposition, iron transporters, hemochromatosis, HFE gene, knockout mice
- MeSH terms
- Solute Carrier Family 11, Member 2, Animals, Erythropoiesis, Female, Heterozygote, Homozygote, Intestine, Small, Iron, Liver, Mice, Transgenic, Placenta, Pregnancy, Promoter Regions, Genetic, Genes, Reporter, Integrases, Cation Transport Proteins, Iron-Binding Proteins, Mice
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