Interleukin-10 knockout mice do not reliably exhibit macroscopic inflammation: a natural history endoscopic surveillance study

Background: Interleukin (IL)-10 knockout (KO) mice, used as a model for inflammatory bowel disease (IBD), develop chronic enterocolitis. Endoscopy, the gold standard for evaluation of human mucosal health, is not widely available for murine models. We aimed to assess the natural history of left-sided colitis in IL-10 KO mice via serial endoscopies. Methods: BALB/cJ IL10 KO mice underwent regular endoscopic assessments from 2 up to 8 months of age. Procedures were recorded and blindly evaluated using a 4-component endoscopic score: mucosal wall transparency, intestinal bleeding, focal lesions and perianal lesions (0-3 points each). An endoscopic score ≥1 point was considered as the presence of colitis/flare. Results: IL-10 KO mice (N=40, 9 female) were assessed. Mean age at first endoscopy was 62.5±2.5 days; average number of procedures per mouse was 6.0±1.3. A total of 238 endoscopies were conducted every 24.8±8.3 days, corresponding to 124.1±45.2 days of surveillance per mouse (13.6 years cumulative surveillance). Thirty-three endoscopies in 24 mice (60%) detected colitis, mean endoscopy score 2.5±1.3 (range: 1-6.3). Nineteen mice (47.5%) had one episode of colitis and 5 (12.5%) had 2-3 episodes. All exhibited complete spontaneous healing on subsequent endoscopies. Conclusions: In this largest endoscopic surveillance study of IL-10 KO mice, 40% of mice did not develop endoscopic left-sided colitis. Furthermore, IL-10 KO mice did not exhibit persistent colitis and universally exhibited complete spontaneous healing without treatment. The natural history of colitis in IL-10 KO mice may not be comparable with that of IBD in humans and requires careful consideration.