Increased sensitivity to chemically induced colitis in mice harboring a DNA-binding deficient aryl hydrocarbon receptor
Bibliographic record
Abstract
The aryl hydrocarbon receptor (AHR), a transcription factor best known for mediating toxic responses of environmental pollutants, also integrates metabolic signals to promote anti-inflammatory responses, intestinal homeostasis, and maintain barrier integrity. AHR regulates its target genes through direct DNA-binding to aryl hydrocarbon response elements (AHREs) but also through tethering to other transcription factors in a DNA-binding independent manner. However, it is not known if AHR's anti-inflammatory role in the gut requires its ability to bind to AHREs. To test this, we determined the sensitivity of Ahrdbd/dbd mice, a genetically modified mouse line that express an AHR protein incapable of binding to AHREs, to dextran sulfate sodium (DSS)-induced colitis. Ahrdbd/dbd mice exhibited more severe symptoms of intestinal inflammation than Ahr+/+ mice. None of the Ahrdbd/dbd mice survived after the 5-day DSS followed by 7-day washout period. By day 6, the Ahrdbd/dbd mice had severe body weight loss, shortening of the colon, higher disease index scores, enlarged spleens, and increased expression of several inflammation genes, including interleukin 1b (Il-1b), Il-6, Il-17, C-x-c motif chemokine ligand 1 (Cxcl1), Cxcl2, Prostaglandin-endoperoxide synthase (Ptgs2), and lipocalin-2. Our findings show that AHR's DNA-binding domain and ability to bind to AHREs are required to reduce inflammation, maintain a healthy intestinal environment, and protect against DSS-induced colitis.
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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 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".