1. Modeling Crohn’s Disease

2. Crohn’s disease usually presents in early adulthood. Patients have a markedly reduced quality of life and a 5 to 7-fold increased risk for developing colorectal cancer. Currently no cure & cause is poorly understood.

3. Canterbury Prevalence of CD: 155 / 100 000 Incidence of CD: 16.5 / 100 000 Gearry et al. 2006

4. MAP is the causative agent of Johne’s disease in ruminants. Johne’s disease is characterised by chronic intestinal inflammation. Studies report increased molecular & microbiological evidence of MAP in Crohn’s disease patients. Does MAP infection have a role in the aetiology of Crohn’s disease? Mycobacterium avium subspecies paratuberculosis (MAP)

5. Model: Interleukin-10 gene-deficient mice Rationale for using this model  Normal intestinal epithelium provides a barrier relatively impermeable to luminal constituents.  Patients with IBD experience enhanced intestinal permeability that correlates with degree of injury. IL10 -/- mice develop a primary intestinal permeability defect in response to enteric microflora.

6. IL10 -/- mice Uninfected (naïve) (Mice 1-10) Infected (challenged with MAP) (Mice 11-20) Specific pathogen free (SPF) mice Housed in micro-isolator cages Assessed weekly for 20 weeks

7. Crohn’s Disease Activity Index (CDAI) Weight loss > 5% Diarrhoea Excreted perianal mucous Rectal prolapse

8. MouseJejunumAsc. colonCaecumDesc. colonTOTALLymph nodeLiver 10111300 21111400 314411011 41011300 51240711 60020220 70010100 80120300 91010200 14421133 0120300 1201 0100 131021410 140010100 1523411033 162210501 170120300 180020200 191111401 200010100 Inflammation score: 0 - 4 Uninfected Infetced

9. Mouse 15Mouse 4 Potential model of inflammation-induced colon cancer.