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 distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.006 | 0.007 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".