Giving Mice the Nod

Science's STKE  08 Feb 2005:
Vol. 2005, Issue 270, pp. tw58
DOI: 10.1126/stke.2702005tw58

The detection of bacteria in the gut by the immune system is regulated, in part, by the Nod proteins, which recognize peptidoglycan motifs from bacteria, and there is a strong association of the inflammatory bowel disorder Crohn's disease with mutations in the Nod2 gene. Nevertheless, questions remain about the normal physiological role of the Nod proteins in maintaining homeostasis in the gut and how impaired Nod function leads to inflammation. Maeda et al. observed that Nod mutations in mice, corresponding with those carried by Crohn's disease patients, increased susceptibility to intestinal inflammation caused by the bacterial cell wall precursor muramyl dipeptide. Kobayashi et al. generated Nod2-deficient mice. Although these animals did not spontaneously develop intestinal inflammation, they were more susceptible to oral infection with the bacterial pathogen Listeria monocytogenes. Production of a group of mucosal anti-microbial peptides was particularly diminished in Nod2-deficient animals, which suggests that a similar defect may contribute to inflammatory bowel disease in humans.

S. Maeda, L.-C. Hsu, H. Liu, L. A. Bankston, M. Iimura, M. F. Kagnoff, L. Eckmann, M. Karin, Nod2 mutation in Crohn's disease potentiates NF-κB activity and IL-1ß processing. Science 307, 734-738 (2005). [Abstract] [Full Text]

K. S. Kobayashi, M. Chamaillard, Y. Ogura, O. Henegariu, N. Inohara, G. Nuñez, R. A. Flavell, Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 307, 731-734 (2005). [Abstract] [Full Text]