Establishment of a mouse model of inflammatory bowel disease using dextran sulfate sodium.

BACKGROUND

Dextran sulfate sodium (DSS)-induced murine colitis is the most commonly used model for the analysis of the pathogenesis of inflammatory bowel disease (IBD) and for the assessment of the efficacy of putative therapeutics. It has been suggested that mice should be given 2.5-10% DSS for 3-7 days to establish the model.

OBJECTIVES

To compare the IBD model in C57BL/6J mice given free access to water containing DSS at concentrations of 2.0%, 2.5% or 3.0% for 5, 7 or 10 days.

MATERIAL AND METHODS

Female mice (9 weeks old) were given access to drinking water containing DSS (2.0%, 2.5% or 3.0%) for 5-10 days. Body weight and colon length were then measured. Signs of edema, epithelial layer disruption, inflammatory cell infiltration, and cytokine induction, and severe colitis-related clinical signs were observed and analyzed.

RESULTS

Weight of the mice decreased and disease activity index (DAI) score immediately increased in all 3 groups. The colon of mice in the 3.0% DSS group was shortened after 5 days, and the colon of mice in the 2.0% and 2.5% DSS groups was shortened after 7 days. A significantly increased intestinal injury score was observed on day 5 in the 3.0% DSS group, on day 7 in the 2.5% DSS group and on day 10 in the 2.0% DSS group. Cytokines were found to be elevated in all 3 groups after 5 days of DSS exposure, with higher DSS concentrations and longer administration times found to be associated with more serious inflammation of the intestinal tract. After 10 days of DSS administration, all mice in the 3.0% DSS group died.

CONCLUSIONS

It took 10 days for the 2.0% DSS group, 5 days for the 3.0% DSS group and 7 days for the 2.5% DSS group to develop obvious observable changes related to the induction of the IBD model. The individual differences within groups (within 10 days) could be reduced by prolonging the administration time. Excessive DSS concentration and longer DSS administration time (exceeding 7 days) may increase mortality of the mice.