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Establishment of Dextran sodium sulfate (DSS) Ulcerative Colitis Model

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

Fig1. The development of the DSS ulcerative colitis model

 

1. Characteristics of the UC model constructed by DSS

2. Advantages of the DSS UC Model

3. DSS UC model construction example

4. Modelling success evaluation criteria

5. Links to this resource

6. Successful case for modeling with Yeasen DSS

7. FAQs

8. Product order

9. Published articles with our reagents

10. Regard Reading

 

1. 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 the 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

 

2. Advantages of the 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 by controlling the administrated DSS dose, which was unique for the 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. The IBD-induced colitis-associated cancer (CAC) model can be created with the combined use of azoxymethane (AOM).

 

3. DSS UC model construction example

3.1 mouse model

(Click 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, was observed after HE staining.

Fig.2 HE staining results of DSS acute colitis sections [1]

3.2 Zebrafish model

(Click 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 observed.

Fig.3 DSS induces an inflammatory response in zebrafish liver

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

3.3 Pig model

(Click 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]

3.4 Drosophila model

(Click 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 a daily change of culture bottle;

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

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

3.5 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] .

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

            

4. Modelling success evaluation criteria

4.1 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

4.2 Histological Change Score

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

Table 3 Histological change score

Sore Ulcer

 

Ulcer ( s )         

 

Epichanges inflammatory

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 muscular 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

>

4.3 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.

4.4 Summary

Preliminary experiments are recommended for using the DSS UC animal model with appropriate control. 8-10 animals per group are minimal requirements. DAI is the criteria to evaluate the results from a preliminary study.

 

5. 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.

 

6. 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

 

7. FAQs

Regardless of the 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

 

8. Product order:

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

Table 6 Product Order

Product name

Article Number

 

Specification

 

Dextran sulfate sodium salt for modeling colitis MW: 36000~50000

60316ES25

25g

Dextran sulfate sodium salt for modeling colitis MW: 36000~50000

60316ES60

100 g

Dextran sulfate sodium salt for modeling colitis MW: 36000~50000

60316ES76

500 g

Dextran sulfate sodium salt for modeling colitis MW: 36000~50000

60316ES80

1 kg

 

9. Published articles with our reagents:

2022

[1]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
[2]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
[3]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
[4]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
[5]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

[1]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
[2]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
[3]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
[4]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
[5]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
[6]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

[1]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
[2]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
[3]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

Before 2020

[1] Oehlers SH, Flores MV, Hall CJ, Crosier KE, Crosier PS. Retinoic acid suppresses intestinal mucus production and exacerbates experimental enterocolitis. Dis Model Mech. 2012 Jul;5(4):457-67. IF=4.973
[2] 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. IF=6.048
[3] Karpowicz , P., Perez, J. & Perrimon , N.,. The Hippo tumor suppressor pathway regulates intestinal stem cell regeneration. Development (Cambridge, England), 2010,137(24), pp.4135–4145. IF=6.868
[4] 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. IF=3.943

Regard Reading

Establishment of Azoxymethane (AOM) and Dextran Sulfate Sodium (DSS) Induced Colitis-Associated Cancer Model

The protocol of Ulcerative Colitis Zebrafish Modeling using Dextran sodium sulfate (DSS)

The protocol of Ulcerative Colitis Drosophila Modeling using Dextran sodium sulfate (DSS)

The protocol of Ulcerative Colitis Piglet Modeling using Dextran sodium sulfate (DSS)