Cdcs1, a Major Colitogenic Locus in Mice, Regulates Innate and Adaptive Immune Response to Enteric Bacterial Antigens

Induction of Bacterial Antigen-Specific Colitis by a Simplified Human Microbiota Consortium in Gnotobiotic Interleukin-10 −/− Mice

“…These results agree with previous reports demonstrating that B6 mice are relatively resistant to colitis in multiple models of acute and chronic intestinal inflammation, whereas 129 mice are highly colitogenic (24)(25)(26). Although the exact genetic loci responsible for colitis susceptibility have not been identified completely in murine models (27,28), our data confirm that the host genetic background has a strong influence on the aggressiveness of colitis and demonstrate differential genetic susceptibility to chronic bacterium-induced, immune-mediated colitis.…”

The fundamental basis of inflammatory bowel disease

“…However, the data at hand is equally consistent with the views that many bacterial antigens elicit responses from a dysregulated immune system and that the anti-flagellin response seems dominant only because it is a powerful antigen that rapidly assumes prominence in an autoreactive milieu. Indeed, this interpretation is favored by recent evidence that C3H/HeJBir mice bear a genetic locus on chromosome 3 harboring an as yet unidentified gene that gives rise to increased T cell responses to colonic bacterial antigens as well as flagellin (38).…”

New pathophysiological insights and modern treatment of IBD

“…Thus, many of the mouse models appear to be more important for identifying pathways of susceptibility rather than for establishing strict pathogenetic associations. For example, on the basis of the observation that C3H/HeJ are highly susceptible colitis mouse strains and C57BL/6 strains, in contrast, are relatively resistant, quantitative trait locus analyses in IL-10-deficient mice identified a colitis susceptibility gene locus on murine chromosome 3 (Cdcs1) that appears to regulate the magnitude of innate responses to Toll-like receptor (TLR) ligands [20,21]. Moreover, investigation of the spontaneously ileitic SAMP1/YitFc mouse identified a susceptibility locus on chromosome 9 that encompasses candidate genes encoding IL-18 and the IL-10 receptor-chain [22].…”