MTHFD1 formyltetrahydrofolate synthetase deficiency, a model for the MTHFD1 R653Q variant, leads to congenital heart defects in mice
Bibliographic record
Abstract
BACKGROUND: A single nucleotide polymorphism (SNP) in the synthetase domain of the trifunctional folate-dependent enzyme MTHFD1 (c.1958G>A, R653Q) has been linked to adverse pregnancy outcomes, neural tube defects, and possibly congenital heart defects. Maternal folate deficiency may also modify the risk associated with these disorders. We recently established a mouse model with a mild deficiency of 10-formyltetrahydrofolate synthetase activity in MTHFD1 (Mthfd1S(+/-) mice) to investigate disorders associated with SNPs in this gene. The effect of synthetase deficiency on embryonic heart development has not yet been examined. METHODS: Female Mthfd1S(+/+) and (+/-) mice were placed on control and folate-deficient diets for 6 weeks before mating to Mthfd1S(+/-) males. Embryos and placentae were collected at embryonic day 14.5. Embryos were evaluated for congenital heart defects by histological examination. RESULTS: Embryonic Mthfd1S(+/-) genotype was associated with an increased incidence of heart defects, primarily ventricular septal defects. Other markers of embryonic development (crown-rump length, embryonic weight, embryonic delay, placental weight, and thickness of the ventricular myocardium) were not affected by embryonic genotype. Maternal genotype and diet did not have a significant effect on these outcomes. CONCLUSION: Deficiency of the MTHFD1 10-formyltetrahydrofolate synthetase activity in embryos is associated with increased incidence of congenital heart defects.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.008 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".