Postnatal cerebellar defects in mice deficient in methylenetetrahydrofolate reductase
Bibliographic record
Abstract
Patients with severe deficiency of methylenetetrahydrofolate reductase (MTHFR) suffer from a wide variety of neurological problems, which can begin in the neonatal period. MTHFR is a critical enzyme in folate metabolism; the product of the MTHFR reaction, 5-methyltetrahydrofolate, is required for homocysteine remethylation to methionine and synthesis of S-adenosylmethionine (SAM). To understand the mechanisms by which MTHFR deficiency leads to significant neuropathology, we examined early postnatal brain development in mice with a homozygous knockout of the Mthfr gene. These mice displayed a dramatically reduced size of the cerebellum and cerebral cortex, with enlarged lateral ventricles. Mthfr deficiency affected granule cell maturation, but not neurogenesis. Depletion of external granule cells and disorganization of Purkinje cells were mainly confined to the anterior lobules of mutant cerebella. Decreased cellular proliferation and increased cell death contributed to the granule cell loss. Reduced expression of Engrailed-2 (En2), Reelin (Reln) and inositol 1,4,5-triphosphate receptor type 1 (Itpr1) genes was observed in the cerebellum. Supplementation of Mthfr(+/-) dams with an alternate methyl donor, betaine, reduced cerebellar abnormalities in the Mthfr(-/-) pups. Our findings suggest that MTHFR plays a role in cerebellar patterning, possibly through effects on proliferation or apoptosis.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".