Semi-Acute Dextran Sulfate Sodium (DSS)-Induced Colitis (10-21 Day)

Description

The DSS-induced colitis model is among the most published IBD models in the field, and is frequently used in drug development. It presents with neutrophilic immune infiltrate and compromised mucosal barrier integrity. DSS can be utilized in mice or rats depending on experimental needs. Colitis is induced via exposure to DSS-treated drinking water. In mice, weight loss is observed thereafter and depending on the study duration, can ultimately recover and return to baseline. In rats, a reduction in weight gain is typically observed vs. overt weight loss. Colitis remains robust through the experimental duration and studies can be terminated during the acute or semi-chronic phase of the model. In mice, test article responses can be compared to the effects of Anti-IL-12-p40 mAb.

  • Advantages: compromised mucosal barrier integrity, flexible treatment window, well-published, validated lots of DSS at BioModels.
  • Disadvantages: difficult to support BID oral dosing during disease induction, model is sensitive to environmental influences, lot-to-lot variations in DSS.
Model Systems
  • C57Bl/6 Mice
  • Sprague-Dawley Rats
Standard Readouts
  • Percent weight change
  • Disease Activity Index: diarrhea and blood in stool scoring
  • Endoscopy: colitis severity and stool consistency scoring
  • Terminal colon weight and length measurement
  • Terminal histopathology and/or IHC analyses
Additional Readouts
  • Colon cytokines
  • Colon myeloperoxidase (MPO)
  • Fecal LCN2, calprotectin, & MPO
  • Peripheral lymphoid organ immunophenotyping
  • Intestinal lamina propria immunophenotyping
  • Custom assays
Representative DataClick Image to Enlarge
Percent Weight Change in the Murine DSS Colitis Model

DSS-induced animals are weighed daily, and body weight change as compared to Day 0 is calculated. The AUC is calculated to compare treatment arms and is shown in the inset. (**p<0.01; ***p<0.005 compared to the vehicle-control).

Composite Disease Activity Index in the Murine DSS Colitis Model

DSS-induced animals are assessed daily for weight loss, diarrhea, and blood in stool phenotypes. Each phenotype is scored and used to calculate the composite Disease Activity Index score. The AUC is calculated to compare treatment arms and is shown in the inset. (***p<0.005 compared to the vehicle-control).

Endoscopy in the Murine DSS Colitis Model

DSS-induced animals are assessed for colonic inflammation and ulceration by video endoscopy and are scored for colitis severity (left) and stool consistency (right). (*p<0.05; ****p<0.001 compared to the vehicle-control).

Colon Weight: Length Ratio in the Murine DSS Colitis Model

Following euthanasia, the colon is excised, measured, rinsed, and weighed; the colon weight:length ratio is calculated. (****p<0.001 compared to the vehicle-control).

Colon Histopathology in the Murine DSS Colitis Model

H&E stained slides from mouse colon tissue are evaluated with light microscopy by an ACVP board-certified veterinary pathologist (Dallas Tissue Research). Features of inflammation, necrosis/gland loss, erosions, submucosal edema, and epithelial hyperplasia are given an individual score and scores are added together to obtain a sum score. Naïve is shown in upper left and diseased is shown in lower left. (****p<0.001).

Colon Lamina Propria Neutrophils in the Murine DSS Colitis Model

Colon samples are digested for leukocyte enrichment, stained, and are assessed via Flow Cytometry for neutrophils. (*p<0.05).

Peripheral Lymphoid Organ Neutrophils in the Murine DSS Colitis Model

Spleen and mLN samples are dissociated, stained, and assessed via Flow Cytometry for neutrophils. Analysis for additional cell types is available. (**p<0.01; ****p<.0001).

Colon Cytokines in the Murine DSS Colitis Model

Colon samples are homogenized and assessed via multiplex cytokine analysis for IFNγ, IL-1β, IL-6, IL-17, KC, and TNFα. Additional cytokines are available.

Daniel Lichtman

Managing Partner