Ever since the first report in 1985 by Japanese scholars using dextran sulfate sodium (DSS) to establish a colitis model in mice, extensive data have shown that the etiology, clinical symptoms, pathological changes, and treatment response of DSS-induced colitis models are similar to human ulcerative colitis (UC). Therefore, the DSS colitis model has become an important tool for studying the etiology, pathogenesis, and tumor diseases of UC, making it one of the most widely used UC models to date.
Figure 1. Developmental Course of DSS-Induced Colitis Model
1. DSS Modeling
DSS is a polyanionic derivative of dextran, formed by the esterification reaction of dextran and chlorosulfonic acid, with a molecular formula of (C6H7Na3O14S3)n and a molecular weight ranging from 36,000 to 50,000, with a sulfur content generally between 17% and 20%. DSS is commonly used to induce colitis models, although its induction mechanism is not yet fully understood. Current research mainly suggests that DSS increases intestinal permeability, disrupts the intestinal mucosal barrier, upregulates certain cytokines (tumor necrosis factor, interleukins, interferons, IL-10, and IL-12), activates certain pathways (NF-κB pathway and TRPV1 pathway), or causes dysbiosis of the intestinal microbiota. Depending on the administration time and administration cycle, colitis models can be divided into acute and chronic models.
Chronic Colitis Modeling
Chronic colitis models can be established using low concentrations of DSS but require a longer administration time. For example, mice can be given 1% to 3% DSS in drinking water for several weeks. The chronic colitis model exhibits: shortened colon length in mice, epithelial hyperplasia, mucosal fibrosis, and lymph node enlargement; a small percentage of animals may show granulation tissue hyperplasia and tumor-like changes.
Acute Colitis Modeling
Acute colitis modeling is also one of the commonly used colitis models due to its simplicity, high success rate, and similarity to human UC lesions, making it an ideal model for studying the pathogenesis of UC and evaluating drug efficacy. Acute modeling generally uses higher concentrations of DSS for a shorter duration. For example, mice can be given 3% to 5% DSS in drinking water for one week. Characteristics of acute phase colitis models include: colon congestion, edema, shortening, brittleness, increased weight-length ratio, varying degrees of colonic ulcers, mucosal edema, loss of goblet cells, crypt distortion and destruction, varying degrees of inflammatory cell infiltration in the mucosa and submucosa, and epithelial cell damage.
Figure 2. Chronic and Acute DSS-induced Colitis Models
2. Types of DSS Models – Mice, Zebrafish, Pigs, Fruit Flies, etc.
In fact, besides mice, other animals such as zebrafish, rabbits, guinea pigs, pigs, and monkeys can also be used to create colitis models using DSS. Research has shown that there are some differences in DSS concentration and modeling period among different species during the modeling process.
Mouse Modeling
1. BALB/c mice, female, 6-8 weeks, 25 g;
2. Prepare 3% DSS drinking water using sterile water and filter it through a 0.22 μm membrane;
3. Allow mice to drink continuously for 7 days, followed by HE staining;
4. Experimental results: Tissues of mice exhibit edema and congestion, with evident signs of inflammation.
Figure 3. HE Staining Results of Acute Colitis Colon Sections Induced by DSS
Zebrafish Modeling
1. Cultivate zebrafish embryos in E3 embryo culture medium containing methylene blue at 28.5°C until 1 day post-fertilization (dpf).
2. Prepare 0.5% DSS drinking water using E3 culture medium and filter it through a 0.22 μm membrane.
3. Treat zebrafish with 0.5% DSS from 3 dpf to 6 dpf.
4. Experimental results: Treatment with 0.5% DSS leads to a darker color in the zebrafish liver and induces inflammatory stress.
Figure 4. DSS-induced Inflammatory Response in the Liver of Zebrafish
Pig Modeling
1. Yorkshire piglets aged four to five days: Experimental group received DSS infusion, while the control group received saline infusion.
2. Each piglet received a daily dose of 1.25g DSS/kg for 5 days via infusion.
3. Experimental results: After DSS infusion, the plasma D-mannitol uptake rate in the experimental group was significantly higher than that in the control group, indicating visible signs of enteritis in piglets.
Figure 5. DSS-induced Increase in D-Mannitol Concentration in the Blood of Piglets
Fruit Fly Modeling
1. Place female fruit flies aged 5-10 days in a small vial measuring 2.5×2.5×1cm, containing feeding medium made of 3.75-cm chromatography paper (Fisher) moistened with a 5% sucrose solution.
2. Prepare feeding media containing different components, including 3% DSS and 25μg/ml bleomycin, using a 5% sucrose solution.
3. Transfer fruit flies into vials containing the chromatography paper and culture them at 29°C for three days. During this period, transfer surviving fruit flies to empty vials containing fresh feeding medium daily.
4. Experimental results: DSS exhibits lethal effects and induces proliferation of intestinal stem cell precursor cells (ISCs).
Figure 6. DSS-induced Proliferation of Intestinal Stem Cell Precursor Cells (ISCs) in Fruit Flies
FAQ
Currently, Arcegen Biology provides dextran sulfate sodium (DSS, MW: 36000~50000) specifically designed for modeling chronic and acute colitis. It boasts high quality, purity, and excellent repeatability. Customers can adjust the concentration and administration time of DSS according to their experimental purposes to establish acute, chronic, and acute-chronic alternating models. The modeling process is simple, cost-effective, and exhibits good repeatability. The success of modeling largely depends on the DSS concentration, molecular weight, administration time, and species of animals.
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Q |
A |
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How to prepare the DSS solution? |
Prepare the DSS solution by dissolving it in sterile water to the desired concentration, and it is recommended to use a 0.22 μm filter. |
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What are the DSS modeling schemes? |
DSS modeling can be achieved through free drinking, oral administration, or gavage. |
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What are the key factors affecting the success of DSS modeling? |
Key factors include DSS concentration, molecular weight, administration time, and animal species. |
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What is the daily water intake volume for rats and mice (including acute and chronic modeling)? |
Mice (20~25g) drink 7-10 milliliters per day each, and rats (100g) drink 10-11 milliliters per day each. |
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DSS and TNBS are both colitis models, what are the differences between the two? |
DSS induces ulcerative colitis, while TNBS induces Crohn's disease colitis. |
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Why is the second stage of chronic colitis modeling always slower than the first stage? |
After the first stage induction, the tolerance to DSS increases, and it is common for symptoms to appear slowly or be milder. To shorten the second stage induction period, the DSS concentration can be appropriately increased. |
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High mortality rate in mice.
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Reason: DSS concentration is too high. Recommendation: Reduce the DSS administration concentration appropriately. |
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Mice show no or low symptoms of colitis. |
Reason: DSS concentration is too low. Recommendation: Increase the DSS administration concentration appropriately; or reduce the interval between cycles (10-14 days). |
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Significant differences in colitis symptoms among mice in the same group. |
Reasons: 1. Bottle cap blockage; 2. Some mice do not drink DSS or drink it in small amounts. Recommendations: 1. Check the mouse water bottles daily; 2. Isolate each mouse individually for culture and check the daily water intake of each mouse. |
Published Articles
[1] Gao X , Fan W , Tan L , et al. Soy isoflavones ameliorate experimental colitis by targeting ERα/NLRP3 inflammasome pathways[J]. The Journal of Nutritional Biochemistry, 2020, 83.
[2] Oehlers SH, Flores MV, Hall CJ, Crosier KE, Crosier PS. Retinoic acid suppresses intestinal mucus production andexacerbates experimental enterocolitis. Dis Model Mech. 2012 Jul;5(4):457-67.
[3] Kim CJ, Kovacs-Nolan JA, Yang C, Archbold T, Fan MZ, Mine Y. l-Tryptophan exhibits therapeutic function in a porcine model of dextran sodium sulfate (DSS)-induced colitis. J Nutr Biochem. 2010 Jun;21(6):468-75.
[4] Karpowicz, P., Perez, J. & Perrimon, N., 2010. The Hippo tumor suppressor pathway regulates intestinal stem cell regeneration. Development (Cambridge, England), 137(24), pp.4135–4145.
[5]Fan H, Chen W, Zhu J, et al. Toosendanin alleviates dextran sulfate sodium-induced colitis by inhibiting M1 macrophage polarization and regulating NLRP3 inflflammasome and Nrf2/HO-1 signaling[J]. International immunopharmacology, 2019, 76: 105909.
[6] Gao X , Fan W , Tan L , et al. Soy isoflavones ameliorate experimental colitis by targeting ERα/NLRP3 inflammasome pathways[J]. The Journal of Nutritional Biochemistry, 2020, 83.
[7] Li, Y., Dong, J., Xiao, H., Zhang, S., Wang, B., Cui, M., & Fan, S. (2020). Gut commensal derived-valeric acid protects against radiation injuries. Gut Microbes, 1–18.
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