Modeling Crohn’s Disease. Crohn’s disease usually presents in early adulthood. Patients have a markedly reduced quality of life and a 5 to 7-fold increased.

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Presentation transcript:

Modeling Crohn’s Disease

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.

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

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)

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.

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

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

MouseJejunumAsc. colonCaecumDesc. colonTOTALLymph nodeLiver Inflammation score: Uninfected Infetced

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