Quantitative analysis of small bowel epithelial gaps in IL-10 knockout and control 129 Sv/Ev mice
Bibliographic record
Abstract
The interleukin-10 knockout (IL-10 -/-) mouse is a homozygous IL-10 deficient strain generated on a 129 Sv/Ev genetic background. It is a well-established rodent IBD model that universally develop colitis after weaning at 8 weeks of age. Impaired barrier function has been implicated in the pathogenesis of inflammatory bowel disease. Confocal Endo-Microscopy (CEM) has demonstrated the existence of epithelial cell gaps resulting from cell shedding in the rodent model. We hypothesize that increased epithelial cell shedding, as measured by an increase in epithelial gaps, contributes to the abnormal intestinal permeability in the IL-10 -/- model. In this study, we measured the epithelial gaps normalized for epithelial cells in IL-10 -/- and compared to the background 129 Sv/Ev strain. We performed CEM on 8-week old IL-10 -/- mice (n= 15) and control 129 Sv/Ev mice (n= 10) using previously described methods. We confirmed the presence of minimal intestinal inflammation prior to the onset of colitis symptoms in the IL-10 -/- mice. We consistently imaged both the jejunum, at 10 cm distal to the ligament of Treitz, and ileum, at 10 cm proximal to the cecum, in each animal. In brief, segments of jejunum and ileum were exteriorized. The lumen was cut open the tissue was stained topically with 0.5 mmol/L with acriflavine hydrochloride, and then washed with saline. Cross-sectional images along the z-axis of the tissues (z-stacks) were obtained with the Five 1 Fluorescence in vivo confocal endomicroscopy system (Optiscan Ltd, Victoria, Australia). The cross-sectional images were aligned and the features extrapolated to create a surface relief of the small intestinal segment. Interpolation between the twodimensional (2-D) frames in each stack was performed using a feature-guided, shapebased computer method to adequately manage translation, rotation, and scaling. The three-dimensional (3-D) relief was analyzed to isolate and quantify the shape, extent, and position of the lesions created where cells had been shed (epithelial gap). Cellular features were analyzed from the 3-D reconstruction of cross-sectional images obtained from the rodent small intestine. Adequately imaged villi, defined as en face villi with 75% surface visualized in the CEM images, were used for the analysis. Ten villi from each animal were manually counted for epithelial cells and the number of epithelial gaps. The gap density function is defined as the number of epithelial gaps (gaps) divided by the number of intestinal epithelial cells (cells) counted in the 10 adequately imaged villi (gap density = gaps/cells). The mean number of epithelial cells per villi counted was 290 for control 129 Sv/Ev mice and 218 for the IL-10 -/- mice. The mean gap density (mean ± standard error) was 6.46±1.36 gaps/1000 cells for 129 Sv/Ev mice that were significantly lower than for the IL-10 -/- mice (17.40 ± 2.09 gaps/1000 cells; p<0.01). The epithelial gap density is significantly higher for IL-10 -/- mice compared to control 129 Sv/Ev mice. The significance of increased epithelial gaps in the pathogenesis of inflammatory bowel disease warrants further investigation.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
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".