D'oh! genes and environment cause Crohn's disease

Abstract

Information obtained from genome-wide association studies has cracked open the biology of common chronic diseases by identifying genes that predispose individuals to these disorders. Cadwell et al. (2010) now demonstrate that a viral infection, a toxic insult to the gut, commensal bacteria, and a Crohn's disease susceptibility gene collude to cause inflammatory disease in the mouse gut.

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.