Ascorbic-acid transporter Slc23a1 is essential for vitamin C transport into the brain and for perinatal survival
Open accessAbstract
The only proven requirement for ascorbic acid (vitamin C) is in preventing scurvy, presumably because it is a cofactor for hydroxylases required for post-translational modifications that stabilize collagen. We have created mice deficient in the mouse ortholog (solute carrier family 23 member 1 or Slc23a1) of a rat ascorbic-acid transporter, Svct2 (ref. 4). Cultured embryonic fibroblasts from homozygous Slc23a1(-/-) mice had less than 5% of normal ascorbic-acid uptake. Ascorbic-acid levels were undetectable or markedly reduced in the blood and tissues of Slc23a1(-/-) mice. Prenatal supplementation of pregnant females did not elevate blood ascorbic acid in Slc23a1(-/-) fetuses, suggesting Slc23a1 is important in placental ascorbic-acid transport. Slc23a1(-/-) mice died within a few minutes of birth with respiratory failure and intraparenchymal brain hemorrhage. Lungs showed no postnatal expansion but had normal surfactant protein B levels. Brain hemorrhage was unlikely to be simply a form of scurvy since Slc23a1(-/-) mice showed no hemorrhage in any other tissues and their skin had normal skin 4-hydroxyproline levels despite low ascorbic-acid content. We conclude that Slc23a1 is required for transport of ascorbic acid into many tissues and across the placenta. Deficiency of the transporter is lethal in newborn mice, thereby revealing a previously unrecognized requirement for ascorbic acid in the perinatal period.
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The absence of SVCT2 is incompatible with life.
“The absence of SVCT2 is incompatible with life [69,70].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [70]
The paper reports that mice lacking Slc23a1, the mouse ortholog of Svct2, died within minutes of birth (opening summary). The newborn-genotyping passage also reports no fetal wastage, so the unqualified claim is broader than the demonstrated finding of lethality in newborn mice. (LLM, conf=0.87)
Experimental — accuracy not yet measuredAccording to animal studies, SVCT2 is important for transport of vitamin C from mother to fetus, but SVCT1 likely participates in this process.
“According to animal studies, SVCT2 is also important for the transport of vitamin C from the mother to the fetus, but SVCT1 likely participates in this process [69,70,78].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [70]
The main-text maternal-supplementation results (page unavailable) conclude that fetal Slc23a1, identified in the paper as an ortholog of Svct2, significantly contributes to vitamin C transport from mother to fetus in mice. The paper does not establish that SVCT1 likely participates in that transport; its discussion says the identity of the transporter had been uncertain. (LLM, conf=0.88)
Experimental — accuracy not yet measuredVitamin C is taken up by cells via SVCT2.
“Vitamin C is taken up by the cells via SVCT2 (SLC23A2, Figure 2C), which is a close analogue of SVCT1 with which it shares 65% sequence homology.”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [70]
The absence of SVCT2 in rodents results in very low levels of vitamin C in the brain, emphasizing the importance of SVCT2 for brain vitamin C transport.
“Moreover, the absence of SVCT2 in rodents results in very low levels of vitamin C in the brain, clearly emphasizing the importance of this transport for the brain [69,70].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [70]
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References 26 · Cited by 367
- Authors
- Sotiriou, S., Gispert, S., Cheng, J., Wang, Y., Chen, A., Hoogstraten-Miller, S., Miller, G. F., Kwon, O., Levine, M., Guttentag, S. H., & Nussbaum, R. L.
- Affiliations
- National Institutes of Health (US)
- National Human Genome Research Institute (US)
- Children's Hospital of Philadelphia (US)
- Venue
- Nature Medicine
- Published
- 2002-05
- Volume
- 8
- Issue
- 5
- Pages
- 514-517
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2038561595
- Cited by
- 367
- References
- 26
- Citations by year
- 2026: 3 · 2025: 12 · 2024: 23 · 2023: 17 · 2022: 11 · 2021: 17 · 2020: 17 · 2019: 7 · 2018: 12 · 2017: 19 · 2016: 12 · 2015: 13 · 2014: 26 · 2013: 29 · 2012: 19
- FWCI
- 13.04
- Type
- journal article
- Language
- en
- Open access
- green
- zenodo.org
- Licence
- public-domain
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, public-domain)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Keywords
- vitamin C, SLC23A1, SVCT2, perinatal survival, respiratory failure, cerebral hemorrhage, scurvy, collagen hydroxylation, 4-hydroxyproline, surfactant protein B, embryonic fibroblasts
- MeSH terms
- Animals, Ascorbic Acid, Brain, Female, Embryonic and Fetal Development, Humans, Restriction Mapping, Mice, Knockout, Gene Expression Regulation, Developmental, Genes, Essential, Symporters, Organic Anion Transporters, Sodium-Dependent, Mice, Sodium-Coupled Vitamin C Transporters
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