ArticleThe American journal of clinical nutrition2011
Shmt1 and de novo thymidylate biosynthesis underlie folate-responsive neural tube defects in mice.
Article in The American journal of clinical nutrition, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
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Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 118 citations in OpenAlex.
- Quantitative assessment of maternal biomarkers related to one-carbon metabolism and neural tube defects.Scientific reports · 2015Pooled it
- Liver-Targeted AAV-DJ-hCBS Therapy Achieves Long-Term Correction of Metabolic Imbalance in CBS-Deficient Mice.International journal of molecular sciences · 2026Article
- Dietary folic acid prevents peripheral neuropathy in mouse models of neural tube defects and type 2 diabetes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Multifaceted role of serine hydroxymethyltransferase in health and disease.Molecules and cells · 2025Review
- The Expression ofCells · 2025Article
- Fundamental origins of neural tube defects with a basis in genetics and nutrition.Experimental brain research · 2025Review
- Late-life dietary folate restriction reduces biosynthesis without compromising healthspan in mice.Life science alliance · 2024Article
- Tracing the Diverse Paths of One-Carbon Metabolism in Cancer and Beyond.Cold Spring Harbor perspectives in medicine · 2024Review
- Epigenetic regulation by TET1 in gene-environmental interactions influencing susceptibility to congenital malformations.bioRxiv : the preprint server for biology · 2024Article
- Mitochondrial One-Carbon Metabolism and Alzheimer's Disease.International journal of molecular sciences · 2024Review
- DTYMK is an essential gene in mice and heterozygosity does not cause neural tube defects.Archives of biochemistry and biophysics · 2024Article
- Glycine homeostasis requires reverse SHMT flux.Cell metabolism · 2024Article
- Micronutrient regulation of the DNA methylome.Frontiers in epigenetics and epigenomics · 2024Review
- Folate deficiency reduced aberrant level of DOT1L-mediated histone H3K79 methylation causes disruptive SHH gene expression involved in neural tube defects.Epigenetics & chromatin · 2023Article
- One-carbon metabolic enzymes are regulated during cell division and make distinct contributions to the metabolome and cell cycle progression in Saccharomyces cerevisiae.G3 (Bethesda, Md.) · 2023Article
- Neural Tube Defects and Folate Deficiency: Is DNA Repair Defective?International journal of molecular sciences · 2023Review
- Gene-nutrient interactions that impact magnesium homeostasis increase risk for neural tube defects in mice exposed to dolutegravir.Frontiers in cell and developmental biology · 2023Article
- A quest for genetic causes underlying signaling pathways associated with neural tube defects.Frontiers in pediatrics · 2023Review
- Pathogenesis of neural tube defects: The regulation and disruption of cellular processes underlying neural tube closure.WIREs mechanisms of disease · 2022Review
- Early Life Stage Folic Acid Deficiency Delays the Neurobehavioral Development and Cognitive Function of Rat Offspring by Hindering De Novo Telomere Synthesis.International journal of molecular sciences · 2022Article
9 more citing papers are in PubMed but not listed here.
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8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundFolic acid supplementation prevents the occurrence and recurrence of neural tube defects (NTDs), but the causal metabolic pathways underlying folic acid-responsive NTDs have not been established. Serine hydroxymethyltransferase (SHMT1) partitions folate-derived one-carbon units to thymidylate biosynthesis at the expense of cellular methylation, and therefore SHMT1-deficient mice are a model to investigate the metabolic origin of folate-associated pathologies.
objectivesWe examined whether genetic disruption of the Shmt1 gene in mice induces NTDs in response to maternal folate and choline deficiency and whether a corresponding disruption in de novo thymidylate biosynthesis underlies NTD pathogenesis.
designShmt1 wild-type, Shmt1(+/-), and Shmt1(-/-) mice fed either folate- and choline-sufficient or folate- and choline-deficient diets were bred, and litters were examined for the presence of NTDs. Biomarkers of impaired folate metabolism were measured in the dams. In addition, the effect of Shmt1 disruption on NTD incidence was investigated in Pax3(Sp) mice, an established folate-responsive NTD mouse model.
resultsShmt1(+/-) and Shmt1(-/-) embryos exhibited exencephaly in response to maternal folate and choline deficiency. Shmt1 disruption on the Pax3(Sp) background exacerbated NTD frequency and severity. Pax3 disruption impaired de novo thymidylate and purine biosynthesis and altered amounts of SHMT1 and thymidylate synthase protein.
conclusionsSHMT1 is the only folate-metabolizing enzyme that has been shown to affect neural tube closure in mice by directly inhibiting folate metabolism. These results provide evidence that disruption of Shmt1 expression causes NTDs by impairing thymidylate biosynthesis and shows that changes in the expression of genes that encode folate-dependent enzymes may be key determinates of NTD risk.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.