Recombination between inverted <i>loxP</i> sites is cytotoxic for proliferating cells and provides a simple tool for conditional cell ablation
Bibliographic record
Abstract
The loxP/Cre recombination system is a widely used tool for mouse functional genomics, in particular for in vivo conditional mutagenesis. Depending on the relative orientation and position of loxP sites, Cre-mediated recombination can result in a variety of targeted genomic rearrangements. It was previously reported that loss of the loxP-carrying chromosome can occur when loxP sites are arranged in inverse orientation. By using a chromosome 2 carrying inverted loxP sites, we found that Cre-mediated recombination not only causes chromosomal loss but also triggers apoptosis. We show that targeted recombination between inverted loxP sites (TRIP) triggers cell death specifically in proliferating Cre-expressing cells, and we provide evidence that TRIP is an efficient tool to ablate proliferating cells within genetically defined cell populations. Furthermore, the procedure requires only a simple, one-step intercross but neither the use of toxins nor the additional step of prodrug injection. With the large repertoire of tissue-specific or inducible Cre-expressing transgenes available, TRIP-mediated cell ablation is valuable to investigate the function of a large variety of cell populations in the context of a whole organism, which includes mechanisms underlying organ development and tissue homeostasis.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.004 |
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".