Mouse models for the study of Crohn's disease

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Abstract

Crohn's Disease (CD) is a chronic inflammatory bowel disease (IBD) that can affect any portion of the gastrointestinal tract and can cause significant morbidity. A variety of animal models of both acute and chronic intestinal inflammation have been developed to investigate disease pathogenesis and novel treatment modalities. These include chemically induced, genetically manipulated and immune-mediated models of gut inflammation, each of which possesses similarities to human IBD and offers unique advantages for studying specific aspects of disease pathogenesis. However, the majority of these models are characterized by colitis and, unlike human CD, do not involve the small intestine. More recently, murine models of chronic ileal inflammation have been characterized that spontaneously develop and closely resemble human CD with regard to disease location, histologic features and clinical response to therapy. Two mouse models of experimental ileitis will be discussed in this review: the TNF ΔARE and SAMP1/YitFc strains. Studies using these new models might provide important insight into the pathogenesis of human CD and test the efficacy of potential therapies to treat this devastating disease.

Section snippets

Traditional murine models of CD

Several animal models of intestinal inflammation have been developed using chemical induction, immune cell transfer, or genetic manipulations [3]. Each has unique advantages for characterizing specific biological mechanisms of gut inflammation.

Mouse models of CD ileitis

Two new murine models of Crohn's-like ileitis have been described (Table 1) 19, 20. These models provide exciting systems for investigating the underlying causes of CD and developing novel therapies.

Concluding remarks

The development of several mouse models of intestinal inflammation in recent years has allowed significant progress in our understanding of the mechanisms involved in chronic intestinal inflammation. Each animal model described under the four different categories of chemically induced, immunologically mediated, genetically manipulated and spontaneous models contribute valuable information regarding potential mechanisms involved in the initiation and perpetuation of chronic gut inflammation. One

Acknowledgments

We thank G. Kollias, S. Matsumoto, S.M. Cohn, M. McDuffie and K.F. Ley for their contributions to the development and characterization of TNF ΔARE and SAMP1/YitFc mice. The studies described in this article were supported by NIH grants DK42191, DK55812 and DK07769 to F.C.

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