Figure 1.

Environmental and Genetic Factors Required for Crohn's-like Disease in Mice

An allele of the human autophagy gene ATG16L1 predisposes individuals to an inflammatory bowel disorder, called Crohn's disease. Patients homozygous for this disease allele display morphological abnormalities in the granules of their specialized gut epithelial cells, called Paneth cells (Cadwell et al., 2008).

(Top) Cadwell et al. (2010) now show that in a mouse model of Crohn's disease in which the mouse Atg16L1 ortholog is disrupted, the Paneth cells have a normal phenotype when the mice are raised in virus-free enhanced barrier facilities.

(Bottom) However, in conventional living conditions these mutant mice are infected with norovirus and develop similar abnormalities in the Paneth cells as those observed in patients with Crohn's disease. This pathology also depends on the interactions of commensal bacteria, the gut innate immune system, and the production of proinflammatory cytokines.