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Modeling Crohn’s Disease

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 / 100 000

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Modeling Crohn’s Disease

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  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. Mycobacterium avium subspecies paratuberculosis (MAP) 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?

  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. Uninfected Infetced Inflammation score: 0 - 4

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

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