A Novel Mouse Model with Targeted and Inducible Deletion of Intestinal CTP:Phosphocholine Cytidylyltransferase α
Bibliographic record
Abstract
Phosphatidylcholine (PC) is the primary phospholipid in mammalian cell membranes, bile, lipid droplets and plasma lipoproteins, and also serves as a precursor for signalling molecules. PC is produced from choline by the CDP‐choline (Kennedy) pathway in all nucleated cells, and the enzyme CTP: phosphocholine Cytidylyltransferase (CT) regulates flux through the pathway. CTα is the predominant isoform in most major tissues, including the liver and intestine. CTα is an important regulator of very‐low density lipoprotein (VLDL) and high‐density lipoprotein (HDL) metabolism the liver. CT also functions to maintain the structural integrity of membranes and to incorporate fatty acids into lipid droplets to avoid cell toxicity, roles which may be particularly important in the intestine which sees large quantities of dietary lipid. However, our understanding of the role of CT and PC in intestinal lipid and lipoprotein metabolism is incomplete. To determine the functional importance of CTα in regulating intestinal lipid and lipoprotein metabolism in vivo , we have generated mice in which we can induce partial (CTα −/+ ) or complete (CTα −/− ) deletion of CTα using a tamoxifen‐inducible Cre‐Lox system. Preliminary data suggest that CTα +/− mice have altered levels of PC in the intestine and impaired chylomicron secretion as compared to controls with normal intestinal CTα activity. Surprisingly, plasma triglyceride was also increased in CTα +/− mice. Future studies will investigate the compensatory mechanisms in the intestine in response to impaired PC supply. Support or Funding Information NSERC and CIHR
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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 | 0.000 |
| 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 | 0.001 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.003 | 0.004 |
| Insufficient payload (model declined to judge) | 0.007 | 0.003 |
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".