Variable In Vivo Embryoprotective Role for Ataxia-Telangiectasia–Mutated against Constitutive and Phenytoin-Enhanced Oxidative Stress in Atm Knockout Mice
Bibliographic record
Abstract
Knockout mice lacking the ataxia-telangiectasia-mutated (Atm) protein exhibit impaired detection and repair of DNA damage and increased embryopathies from ionizing radiation in vivo, and vehicle or phenytoin in embryo culture. Here we determined if Atm-deficient mice are more susceptible in vivo to phenytoin embryopathies. Wild-type (+/+) or heterozygous (+/-) Atm knockout dams were mated with +/- males, pregnant dams were treated with phenytoin (65 mg/kg ip) or its vehicle, and resorptions and fetuses were genotyped and characterized. This strain proved resistant to phenytoin-initiated cleft palates but not to other spontaneous and phenytoin-enhanced embryopathies. With vehicle-treated +/- dams, fetal body weight was lower in homozygous Atm-null (-/-) fetuses compared to +/- and +/+ littermates (p < 0.05). Phenytoin enhanced this Atm-dependent embryopathic pattern (p < 0.05). It also enhanced DNA oxidation in -/- Atm-deficient embryos compared to its +/- Atm-deficient (p < 0.001) and +/+ Atm-normal (p < 0.001), phenytoin-exposed littermates and to its -/- vehicle controls (p < 0.01). Postpartum lethality was greater in both +/- and -/- Atm-deficient fetuses compared to +/+ littermates, independent of treatment (0.05 < p < 0.1). By maternal genotype, +/- Atm-deficient dams had fewer implantations than +/+ dams, independent of treatment, and phenytoin decreased litter size (p < 0.05). Conversely, phenytoin-exposed +/+ fetuses were more likely than -/- littermates to die in utero (p < 0.05), and in +/+ dams fetal resorptions and postpartum lethality were variably higher and enhanced by phenytoin (p < 0.05). Despite variable actions in vivo, the embryoprotective effects of Atm suggest a role for reactive oxygen species and oxidative DNA damage in some spontaneous and phenytoin-enhanced embryopathies.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".