Insights into phosphatidylcholine biosynthesis and function from gene targeting in mice
Bibliographic record
Abstract
The biosynthesis of phosphatidylcholine (PC) via choline was elucidated by Kennedy in the 1950s. In 1960, Bremer described a second pathway in liver catalyzed by phosphatidylethanolamine (PE) N ‐methyltransferase (PEMT). Research in the 1980s revealed regulatory features of PC biosynthesis and most enzymes involved were purified. The genes and cDNAs were cloned in the 1990s that allowed for generation of knockout mice. Pemt −/ − mice fed a chow diet have no phenotype. When fed a choline‐deficient diet, the mice die from liver failure after 3 days. We bred Pemt −/ − mice with mice that lacked MDR2, a protein that exports PC into bile. Strikingly, Pemt −/ − / Mdr2 −/ − mice fed the choline‐deficient diet survived for 90 days. Pemt −/ − / Mdr2 −/ − , but not Pemt −/ − , mice efficiently recycle choline and maintain a normal PC/PE ratio in liver. In Pemt −/ − mice, the hepatic PC/PE ratio decreased to below 1 and caused permeabilization of the cell. Pemt −/ − compared to Pemt +/+ mice fed a high fat/cholesterol diet had decreased levels of lipids in plasma. PEMT deficiency resulted in decreased secretion of very low density lipoproteins (VLDL). When Pemt −/ − mice were bred with atherosclerosis‐prone mice, the lack of PEMT resulted in striking protection from atherosclerosis. Mice with a knockout of hepatic CTP:phosphocholine cytidylyltransferase α survive and maintain normal levels of PC. However, plasma lipid levels are 50% lower than wildtype mice and VLDL secretion from liver is decreased by 50%. It is unlikely that in the 1960s Drs. Kennedy or Bremer would have anticipated the development of knockout mice and the role of PC biosynthesis in liver failure or development of atherosclerosis.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.003 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.003 | 0.005 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
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".