Th2 driven anion conductance in airway epithelium is lost in the mCLCA3 knockout mouse
Bibliographic record
Abstract
Ion transport creates the osmotic drive for appropriate airway hydration, which is essential for mucociliary clearance, the primary lung defense mechanism. Microbial insult or immunological dysregulation results in a strong, Th2‐driven cytokine response, which stimulates fluid secretion and the clearance of mucus and microbes. This response is primarily mediated by an increase in calcium activated chloride conductance. mCLCA3, a putative regulator of calcium activated chloride channels, is highly up‐regulated in asthma. We used mCLCA3 knockout mice to assess the role of this gene in Th2‐induced conductance. Physiologic properties of homozygous, heterozygous knockout mice and wild type mCLCA3 littermates were compared in two preclinical models of asthma. Cohorts were challenged with either recombinant IL‐13 by intranasal administration or whole‐body exposure to ovalbumin (OVA), and short‐circuit current was measured across freshly excised tracheas. The Th2 driven increase in DIDS‐sensitive calcium activated chloride conductance was dependent on mCLCA3 gene dose. Genechip analysis of OVA‐treated knockout and littermate control mice did not reveal any changes in the expression of known channel proteins. Reduced Cl conductance in the mCLCA3 KOs may reduce airway hydration and mucus clearance, thereby explaining, in part, the increase in mucus found in bronchoaveolar lavage of the mCLCA3 knockout mouse under Th2‐challenged conditions. Supported in part by NSERC and the Breathe program of the Canadian CF Foundation 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) | 0.001 | 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) | 0.009 | 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".