SOP 7.18 - Chronic DSS Colitis (Mouse Model)

1. Introduction and Definitions:

Dextran sodium sulfate (DSS) is a molecule that induces colitis like that seen in human patients. It is administered to the animal via their drinking water. This is a common model of Inflammatory Bowel Disease (IBD), the condition of chronic intestinal inflammation that is currently incurable. 

Optimal DSS concentrations are determined by preliminary experiments, as disease severity often varies dependent on animal age, gender, and strain. Standard drinking water is given to controls.

2. Materials:

• Water bottle
• DSS solution
• Lactated Ringer’s solution
• 1-3ml sterile syringes
• Sterile needles (26-27g)
• Alcohol swabs
• Weigh scale

3. Procedures:

• Prior to the initiation of a DSS cycle, all the study mice must be weighed to obtain a baseline weight and it is recorded with the date on the cage card. Based on the baseline weight, the 5%, 10% and 15% weight loss values are calculated (see Appendix 1). 
• DSS is dissolved into standard drinking water to yield the desired (1% - 2%) (“%” = g/100 ml). 
• Regular water bottles are removed from the cage and replaced with the DSS-dosed bottles. 
• DSS is administered in drinking water for 5 days, followed by a return to regular water for 5 days. This cycle is repeated 3 times. 
• Non-standard water bottles are used for the DSS mice, a special request is required and must be submitted to ACS. 

Monitoring:

• Ensure that cages are flagged with specific ACS cage alerts that animals are on a DSS study. 
• Daily monitoring: cages are checked for DSS-water consumption (volume drop in bottle, urine output) and bottles topped up/cages replaced as necessary by lab. 
• Daily weight, appearance, and behavioural changes must be recorded at room level. 
• In the first two (more severe) DSS cycles: All mice in a DSS treated group must receive a daily subcutaneous injection of 1ml lactated Ringer’s solution. Each and every animal requires a new sterile syringe and needle. Refer to SOP 7.9.1 “Subcutaneous Injection Techniques in Mice”. Mice must be weighed before fluid therapy administration. 
• In the third DSS cycle, when clinical symptoms are expected to be less severe, only mice failing to gain weight over a 24-hour period must receive the subcutaneous injections of 1ml lactated Ringer’s solution. 
• Mice may receive 2 daily injections of 1ml lactated Ringer’s solution on the advice of Animal Care Services (ACS) or Veterinary staff. 

Clinical Outcomes:

• Treated mice may develop loose stool or diarrhea with detectable blood in the stool. 
• Mice show ruffled fur and weight loss while the colitis is present. This should begin to resolve by the third DSS cycle. 
• Weight loss should not reach a 15% drop from baseline value, unless approved in the Animal Use Protocol. 
• All humane endpoints as approved in the Animal Use Protocol must be followed. 

Weight Loss Chart