Profound phenotypic variation among mice deficient in the maintenance of genomic imprints
Bibliographic record
Abstract
BACKGROUND: An alteration in the mechanism that maintains the monoallelic, imprinted expression of genes can result in their biallelic expression and lead to disruptions in fetal development. Here, we examined the consequences of a loss of maintenance methylation at one specific stage of preimplantation, induced by a deficiency of the oocyte-derived Dnmt1o protein and known to produce biallelic expression of imprinted genes. METHODS: Phenotypes of mid-gestation Dnmt1o-deficient mouse embryos were assessed by a scoring system based on the developmental stage of 17 anatomical features and by magnetic resonance microscopy. RESULTS: Many mid-gestation embryos developing without Dnmt1o protein exhibited significant developmental delays of multiple organ systems (P < 0.05) and a wide variety of morphologic anomalies compared with wild-type embryos. Most of the remaining mid-gestation Dnmt1o-deficient embryos appeared normal. CONCLUSIONS: These findings indicate that a profound range of gestational phenotypes can be induced by the loss of a single protein at a specific preimplantation developmental stage. This is best explained by the formation of epigenetic mosaic early embryos, composed of somatic cells with different spectra of normal intact genomic imprints. These findings have important implications for understanding the types of embryonic phenotypes related to the disruption of inherited imprints, and thus may provide a model of altered imprinting in humans. In particular, because Dnmt1o functions in the preimplantation embryo, a complete or partial loss of Dnmt1o function may play a role in epigenetic abnormalities seen in assisted reproduction technology births.
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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 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".