Loss of M2 and M3 muscarinic receptor function in double mutant mice eliminates ovalbumin‐induced airway hyperresponsiveness (870.7)
Bibliographic record
Abstract
Mutant murine models lacking specific muscarinic receptor (MR) subtypes are a primary tool to explore MR biology in health and disease, due to the lack of selective antagonists. Since both M2R and M3R subtypes are involved in the vagal control of airway responsiveness (AR; FASEB J 18:711,2004), we examined the impact of combined loss of M2R and M3R function on the development of AHR in M2R ‐/‐ /M3R ‐/‐ double mutant mice. AR was assessed in 12 mutant mice divided into an ovalbumin (OVA) sensitization group (n=6; OVA‐Alum adjuvant i.p. day 0 and 7 plus aerosol exposure days14‐16) and an Alum adjuvant control group (n=6; Alum). Since M2R ‐/‐ /M3R ‐/‐ double mutants show no cholinergic contractile responses, we performed a 5‐hydroxytryptamine (5‐HT) i.v. dose‐response challenge (5‐100 ug/kg) for respiratory system resistance (Rrs) to assess AR and bronchioalveolar lavage (BAL) to assess inflammatory cells. The Rrs response was not different between groups (max increase OVA 339% + 32 sem vs Alum 301% + 28; p>0.05), although the BAL eosinophil count was significantly greater in the OVA group (25% + 5) compared to the Alum (0.1% + 0.08). Our results suggest that M2R/M3R functions are critically involved in the development of OVA‐induced AHR. Grant Funding Source : Supported by Canadian Institutes for Health Research (MOP81211), Intramural Research Pgm NIDDKD, NIH
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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 | 0.002 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.004 | 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".