Establishment of Dextran sodium sulfate (DSS,Colitis Grade) Ulcerative Colitis Model

Development History of DSS Modeling

Drug development requires animal models to test efficacy. With over 50 years of development and optimization, the Dextran Sulfate Sodium Salt (DSS) ulcerative colitis (UC) model, among various animal models, is widely used to study the etiology and pathogenesis of inflammatory bowel disease (IBD).

Fig1. The development of the DSS ulcerative colitis model

Characteristics of the UC model constructed by DSS

Multiple acute or chronic symptoms of UC can be induced, such as diarrhea, mucus-like stool, fecal occult blood, gross bloody stool, weight loss, decreased activity, and poor coat color, by different DSS doses.

Table 1 Histological characteristics of DSS colitis model

DSS colitis model category

acute colitis model

Chronic phase colitis model

histological changes

Colon hyperemia, edema, shortening, brittleness, increased weight-to-length ratio

significantly shortened colon

 

Colon ulcers of varying degrees

Mucosal thickening, lymphadenopathy

Mucosal edema, goblet cell loss, crypt swelling and destruction

goblet cell loss, crypt loss

 

Different degrees of inflammatory cell infiltration in the mucosa and submucosa, epithelial cell damage

Adenomatous polyps and tumor-like changes in a small number of animals

Advantages of DSS UC Model

  1. The protocols are easy to be implemented.
  2. The DSS UC model closely resembles human UC symptoms with high repeatability.
  3. Various characteristic symptoms can be induced through controlling the administrated DSS dose, which was unique for DSS UC model.
  4. The DSS UC model can be generated with a variety of widely used model animals, such as mice, rats, zebrafish, pigs, fruit flies, etc.
  5. IBD-induced colitis associated cancer (CAC) model can be created with combined use of azoxymethane (AOM).

DSS UC model construction example

  1. mouse modelClick for details

1) BALB/c mice, female, 6-8 weeks, 25 g;

2) Sterile drinking water with 3% DSS, and filter with a 0.22 μm membrane;

3) DSS was administrated for 7 days;

4) Inflammation, such as colon edema and congestion, were observed after HE staining.

 

 

  1. Zebrafish modelClick for details
1)Zebrafish embryos were obtained from natural spawning and raised until 1 day post fertilization (dpf) in an incubator at 28.5℃ in recirculating water (60 μg/mL instant ocean sea salts) and supplemented with methylene blue up to 1 dpf;
2)After 1 dpf, use E3 embryo culture medium without methylene blue to culture to 3 dpf;
3)Prepare 10% DSS storage solution with E3 medium;
4)Dilute DSS with culture medium to the maximum non lethal dose (DSS concentration reference: 0.5%);
5)The zebrafish were treated with 0.5% DSS from 3 dpf to 6 dpf, and the indexes were.

Fig.3 DSS induces inflammatory response in zebrafish liver [2]

3.Pig modelClick for details

1) Yorkshire piglets at age of 4-5 days;

2) DSS dose: 1.25g/kg, oral intake for 5 days;

3) Increased D-mannitol uptake rate was observed.

Fig.4 DSS-induced D-mannitol concentration in piglets was higher than that in the control group [3]

4.Drosophila modelClick for details

1) Drosophila,female, 5-10 days;

2) Feeding medium was prepared with 5% sucrose solution containing 3% DSS and 25 μg/mL bleomycin;

3) Drosophila was cultured at 29°C for three days with daily change of culture bottle;

4) DSS induced the proliferation of ISC precursor cells and had lethal effect on drosophila.

Fig.5 DSS induces the proliferation of ISC precursor cells in Drosophila [4] .

 

5.Colitis associated cancer(Click for details

1)BALB/c mice,male,7 weeks old;
2)On day 1, weigh and mark mice. Inject mice intraperitoneally with 10 mg/kg AOM solution.
3) Fill the drinking supply of the mouse cages with water. Calculate 7-10 mL water per mouse per day. Feeding for one week.
4) Replace drinking water with 2.5% DSS for one week;
5) Feed with regular drinking water for two weeks;
6) Repeat steps 3-4 for 3 times.

     

    Fig.6 Schematic diagram of CAC induced by AOM/DSS [5] .

    Model evaluation criteria

    1. Disease Activity Index ( DAI score )

    The model was evaluated with multiple parameters including body weight, fecal viscosity and occult blood, through which generates the overall DAI.

    Table 2 DAI scoring rules

    score

    percent weight loss

    stool consistency

    fecal occult blood

    0

    0

    normal

    Negative

    1

    1-5%

    soft stool

    light blue

    2

    5-10%

    mucoid stool

    blue

    3

    10-20%

    loose stools

    dark blue

    4

    >20%

    \

    gross bloody stool

    1. Histological Change Score

    The scores were given for the above indicators based on the histological changes excluding the lymph node formation for acute colitis model. The HE staining reagents used is Cat#60524ES60.

    Table 3 Histological change score

    score

    Ulcer( s )

    Epithelial changes

    inflammatory infiltrate

    lymph node( s )

    0

    0

    normal

    none

    none

    1

    1

    goblet cell loss

    Pericrypt infiltration

    1

    2

    2

    goblet cell loss

    Infiltration of the muscularis mucosae

    2

    3

    3

    crypt deletion

    General infiltration of the muscularis mucosa, thickening of the mucosa

    3

    4

    >3

    Extensive crypt loss or polypoid regeneration

    submucosa invasion

    >3

    1. Colon length
    The shortened colon length was an obvious phenotype for the chronic colitis model, while similar changes can be detected on day 8 for the acute colitis model.
      4.Summary

      Preliminary experiments are recommended for using DSS UC animal model with an appropriate control. 8-10 animals per group are minimal requirements.

      Links to this resource

      1)Xiaona Gao, et al. Journal of Nutritional Biochemistry 83 (2020) 108438.
      2)Jing Ma,et al.Aquaculture and Fisheries (2021) 548–557.
      3)Connie J. Kim, et al. Journal of Nutritional Biochemistry 21 (2010) 468–475.
      4)Fangfang Ren,et al.PNAS.2010.107 (49) 21064-21069.
      5)Jia-Rong Huang,et al.Frontiers in Pharmacology.2020.11:586885.

        Successful case for modeling with Yeasen DSS

        Successful acute colitis models are generated with Yeasen DSS (Cat#60316ES, MW: 36000~50000) in 7 days with prominent phenotype as shown in the following table.

        Table 4 Construction of different types of enteritis models with DSS

         

        Model

        Modeling samples

        Modeling plan

        Modeling results

        Use evaluation

        acute colitis

        BALB/c mice, female, 6-8 weeks, 25 g

        3%-5% DSS drink freely for 7 consecutive days

        Day 5 appeared, the length of the colon was shortened, HE staining, and the inflammation was obvious

        molding speed is fast and the time is short. Consistent with the characteristics of acute colitis model

        C57BL/6 mice, male, 8 weeks, 20 g

        3%-5% DSS by gavage, continuous administration

        Day 5 occurs, colon shortening, weight loss, blood in the stool, diarrhea

        High mold rate and short duration. Consistent with the characteristics of acute colitis model

        chronic colitis

        C57BL/6 mouse, male, 8 weeks, 22 g

        1-2% DSS by gavage, continuous administration

        Day40 appears, colon shortening, weight loss, blood in the stool, diarrhea

        High molding rate . Consistent with the characteristics of the chronic colitis model

        colon cancer

        C57BL/6 mouse, male, 8 weeks, 21 g

        1%-2% DSS ad libitum for 5 days for 3 weeks

        14 weeks with shortened colon length, weight loss, HE staining, and obvious inflammation

        High molding rate . Consistent with colon cancer model characteristics

         

        FAQs

        Regardless of acute DSS colitis model or chronic DSS colitis model, the severity and success of enteritis are related to mouse species (different genetic backgrounds), DSS concentration, and dosing cycle.

        Table 5 Common problems of DSS colitis modeling

        possible problems

        possible reason

        Suggested solution

        high mortality in mice

        DSS concentration too high

        Decrease the concentration of DSS administered

        Mice with no or low symptoms of enteritis

        DSS concentration too low

        Increase DSS dosing concentration; decrease cycle interval (10-14 days)

        In the same group of mice, the symptoms of enteritis vary greatly

        bottle cap clogged

        Check the mouse drinking bottle daily

        Product order

        Hot-selling product only needs 1/3 of the price of M* with same efficiency,and we keep a large stock.

        Product Name

        Article Number

        Specification

        Dextran Sulfate Sodium Salt (DSS), Colitis Grade MW:36000~50000

        60316ES25/60/76/80

        25 g/100 g/500 g/1 kg

        Azoxymethane (AOM)

        60751ES03/08/10

        1 mg/5 mg/10 mg

        MolPure® Stool DNA Kit

        18820ES08/50/70

        5 T/50 T/200 T

        MolPure® Mag48 Soil/Stool DNA Kit FA

        18528ES48

        48 T

        MolPure®Mag Soil/Stool DNA Kit

        18526ES20/50/70

        20 T/50 T/200 T

        Hematoxylin and Eosin Staining Kit

        60524ES60

        2×100 mL

        Urine Fecal Occult Blood Test Kit

        60403ES60

        100T

        Alcian Blue Periodic Acid-Schiff (AB-PAS) Staining Solution

        60534ES50/60

        6×50 mL/6×100 mL/

        Published articles with our reagents

        2024

        • [1]Zhong D, Jin K, Wang R, ,et al. Microalgae-Based Hydrogel for Inflammatory Bowel Disease and Its Associated Anxiety and Depression. Adv Mater. 2024 Jan 26:e2312275. doi: 10.1002/adma.202312275. IF=29.4
        • [2]Zhang Y, Tu S, Ji X, Wu J, Meng J, Gao J, Shao X, Shi S, Wang G, Qiu J, Zhang Z, Hua C, Zhang Z, Chen S, Zhang L, Zhu SJ. Dubosiella newyorkensis modulates immune tolerance in colitis via the L-lysine-activated AhR-IDO1-Kyn pathway. Nat Commun. 2024 Feb 13;15(1):1333. doi: 10.1038/s41467-024-45636-x.IF= 16.6
        • [3] Xuan ZhangXia GaoXiangzhou Yi,et al. Multi-targeting inulin-based nanoparticles with cannabidiol for effective prevention of ulcerative colitis[J]. Materials Today Bio.2024, 25100965. IF=8.2

        2022

        • Mengmeng Xu, Ying Kong, Nannan Chen,et al.Identification of Immune-Related Gene Signature and Prediction of CeRNA Network in Active Ulcerative Colitis[J].Frontiers in Immunology.2022; 13: 855645.IF=7.561
        • Lujuan Xing, Lijuan Fu, Songmin Cao,et al.The Anti-Inflammatory Effect of Bovine Bone-Gelatin-Derived Peptides in LPS-Induced RAW264.7 Macrophages Cells and Dextran Sulfate Sodium-Induced C57BL/6 Mice[J]. Nutrients 2022, 14, 1479. IF=5.717
        • Wang S,  Huang J,  Tan KS, et al.Isosteviol Sodium Ameliorates Dextran Sodium Sulfate-Induced Chronic Colitis through the Regulation of Metabolic Profiling, Macrophage Polarization, and NF-B Pathway[J].Oxidative Medicine and Cellular Longevity. 2022,4636618.IF=5.076
        • YuangengLi,PingYu,WenwenFu,et al.Polysaccharides from Panax ginseng C. A. Meyer alleviated DSS-induced IBD by inhibiting JAK2/STAT1/NLPR3 inflammasome signalling pathway in mice[J].Journal of Functional Foods.2022, 105013.IF=4.451
        • Lei-NingChen,TaoJing,Zi-BinLin,et al.Metabolomic and transcriptomic responses of mouse testis to the dextran sulfate sodium induced colitis[J].Reproductive Toxicology.2022, Pages 35-42.IF=3.143

        2021

        • Li Zhao, Fei Wang,Zhengwei Cai,et al.Improving drug utilization platform with injectable mucoadhesive hydrogel for treating ulcerative colitis[J].chemical engineering journal.424(2021)130464.IF=16.744
        • Lingjun Tong, Haining Hao, Zhe Zhang,et al.Milk-derived extracellular vesicles alleviate ulcerative colitis by regulating the gut immunity and reshaping the gut microbiota[J].Theranostics.2021; 11(17): 8570-8586 IF=11.556
        • Jingjing Gan, Yuxiao Liu, Lingyu Sun,et al.Orally administrated nucleotide-delivery particles from microfluidics for inflammatory bowel disease treatment[J].Applied Materials Today.2021 Dec;25:101231 IF=10.041
        • JialiDong,YuanLi,HuiwenXiao,et al.Oral microbiota affects the efficacy and prognosis of radiotherapy for colorectal cancer in mouse models[J].Cell reports.2021, 109886.IF=9.423
        • Hao H,  Zhang X,  Tong L,  Liu Q,et al.Lactobacillus plantarumEffect of Extracellular Vesicles Derived From  Q7 on Gut Microbiota and Ulcerative Colitis in Mice[J].Frontiers in Immunology.2021.777147 .IF=7.561
        • Yaohua Fan,Yanqun Fan,Kunfeng Liu,et al.Edible Bird’s Nest Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis in C57BL/6J Mice by Restoring the Th17/Treg Cell Balance[J].Frontiers in Pharmacology.2021.632602.IF=7.561

        2020

        • Li, Y., Dong, J., Xiao, H., Zhang, S., Wang, B., Cui, M., & Fan, S. Gut commensal derived-valeric acid protects against radiation injuries. Gut Microbes,.2020 .1–18.IF=10.245
        • Jia-Rong Huang, Sheng-Te Wang, Meng-Ning Wei,et al.Piperlongumine Alleviates Mouse Colitis and Colitis-Associated Colorectal Cancer[J].Frontiers in Pharmacology.2020.586885.IF=7.561
        • 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.IF=6.048