945: Mucosal Gene Expression Profiles in Canine Inflammatory Bowel Disease
Grant Status: Closed
Grant Amount: $60,000
Albert E. Jergens, DVM, PhD; Iowa State University
June 1, 2008 - December 31, 2011
Sponsor(s): Akita Club of America, Inc., American Boxer Charitable Foundation, American Maltese Association, French Bulldog Club of America, German Wirehaired Pointer Club of America, Keeshond Club of America, Portuguese Water Dog Club of America, Inc., Samoyed Club of America Education & Research Foundation, Soft Coated Wheaten Terrier Club of America, Inc., Soft Coated Wheaten Terrier Genetic Research Fund, Westie Foundation of America, Inc., Worcester County Kennel Club, Yorkshire Terrier Club of America, Yorkshire Terrier Club of America Foundation, Inc.
Breed(s): -All Dogs
Research Program Area: Gastrointestinal Disease
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Project Summary
Canine inflammatory bowel disease (IBD) is a chronic intestinal disorder likely resulting from the interaction between genes and environmental factors. We propose to utilize unique molecular biology tools to: (1) identify key genetic factors contributing to disease expression, (2) characterize gene expression profiles which may predict responsiveness to specific therapies, and (3) provide the framework upon which to facilitate identification of IBD susceptibility genes that predispose specific canine breeds to clinical disease. We are making good progress towards these goals as evidenced by the following: o We have collected samples from a representative heterogeneous population of 18 IBD dogs for comparison to 6 healthy dog tissues. o We have carefully extracted the genetic material (RNA) from endoscopic samples which will be used in our gene profiling studies. o We have now evaluated gene expression profiles in the normal versus diseased dog groups using sophisticated statistical modeling to help us 'tease out' gene expression patterns which discern healthy versus diseased intestinal tissues. It is our expectation to identify specific genes which serve as biomarkers for diagnosing canine IBD and for monitoring the effects of therapy. We have now identified a grouping of 17 'marker' genes that may be more critically assessed in future studies. o We have noted that IBD dogs show differences in intestinal gene expression as compared to healthy dogs; and these differences in expression may help to explain the mechanisms of chronic inflammation in affected dogs. o We have preliminary evidence that changes in the intestinal bacteria accompany the abnormal gene patterns. It is our belief that this association should be explored more fully with additional studies; since this situation is identical to the association between people and their intestinal bacterial populations causing human IBD (i.e., Crohn's disease and ulcerative colitis). o We have now confirmed the expression patterns of select differentially expressed genes in diseased dogs using sophisticated molecular techniques. This suggests that the observations regarding gene expression patterns using the gene chips are accurate. o We have now completed data analysis and have a second publication submitted to PLOS One entitiled "16S rRNA gene pyrosequencing reveals bacterial dysbiosis in the duodenum of dogs with idiopathic inflammatory bowel disease"Publication(s)
Jergens, A., Young, J., Moore, D., Wang, C., Hostetter, J., Augustine, L., … Mosher, C. (2014). Bcl-2/Caspase 3 mucosal imbalance favors T cell resistance to apoptosis in dogs with inflammatory bowel disease. Veterinary Immunology and Immunopathology, 158(3–4), 167–174. https://doi.org/10.1016/j.vetimm.2014.01.004
Suchodolski, J. S., Dowd, S. E., Wilke, V., Steiner, J. M., & Jergens, A. E. (2012). 16S rRNA Gene Pyrosequencing Reveals Bacterial Dysbiosis in the Duodenum of Dogs with Idiopathic Inflammatory Bowel Disease. PLoS ONE, 7(6), e39333. https://doi.org/10.1371/journal.pone.0039333
Suchodolski, J. S., Xenoulis, P. G., Paddock, C. G., Steiner, J. M., & Jergens, A. E. (2010). Molecular analysis of the bacterial microbiota in duodenal biopsies from dogs with idiopathic inflammatory bowel disease. Veterinary Microbiology, 142(3–4), 394–400. https://doi.org/10.1016/j.vetmic.2009.11.002
Wilke, V. L., Nettleton, D., Wymore, M. J., Gallup, J. M., Demirkale, C. Y., Ackermann, M. R., … Jergens, A. E. (2012). Gene expression in intestinal mucosal biopsy specimens obtained from dogs with chronic enteropathy. American Journal of Veterinary Research, 73(8), 1219–1229. https://doi.org/10.2460/ajvr.73.8.1219
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Participate in canine health research by providing samples or by enrolling in a clinical trial. Samples are needed from healthy dogs and dogs affected by specific diseases.
