Disruption of the murine CTP: phosphoethanolamine cytidylyltransferase gene causes embryonic lethality
Bibliographic record
Abstract
The CDP: ethanolamine (Kennedy) pathway is responsible for the de novo biosynthesis of phosphatidylethanolamine (PE) and ethanolamine plasmalogens, where diacyl‐ and alkylacylglycerol are coupled with CDP‐ethanolamine for their production respectively. We have disrupted the mouse gene encoding the rate‐limiting enzyme in this pathway, CTP: phosphoethanolamine cytidylyltransferase (Pcyt2) by replacing a 2.8kb region, including the promoter region and exons 1–3 with a Neomycin cassette. Upon inter‐crossing of Pcyt2+/‐ animals we obtained low litter sizes and unexpected Mendelian frequencies. From a total of 111 pups, 40% Pcyt2+/+ and 60% Pcyt2 +/− and no knockout pups were genotyped. Examination of embryos from E13.5 and E10.5 resulted in similar patterns of distribution, with no knockout embryos identified. This demonstrates that Pcyt2−/− mice are embryonic lethal prior to at least E10.5. Comparative mRNA analyses, immunoblotting and enzyme activity assays between Pcyt2+/− and controls have revealed a tissue specific gene dosage effect with significant differences between Pcyt2+/− and controls (30–50%). In vitro enzyme activities for PE methyltransferase, a liver specific enzyme that converts PE to phosphatidylcholine reveals slightly up‐regulated activities in Pcyt2+/− animals. Phospholipid composition and content of Pcyt2+/− liver, heart and brain show no significant differences from controls. This demonstrates the importance of the Kennedy pathway for the production of ethanolamine phospholipids.
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 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) | 0.004 | 0.001 |
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".