1445: Granulomatous Colitis In Boxer Dogs: Genetic Analysis of Disease and Functional Analysis of Bacterial Killing

Project Summary

Granulomatous colitis (GC) is a severe inflammatory bowel disease (IBD), typically diagnosed in Boxer dogs younger than four years of age. Affected dogs present with hemorrhagic diarrhea, often progressing to weight loss, anemia, hypoalbuminemia, and chronic debilitation. Recent studies have identified invasive Escherichia coli within macrophages in diseased intestinal tissue, and eradication of E. coli induces dramatic clinical and histological improvement. The type of E. coli isolated from GC-affected Boxer dogs is very similar to a new group of adherent and invasive E. coli (AIEC) associated with IBD in people. AIEC are considered opportunistic pathogens that can exploit genetic defects in bacterial killing in an IBD susceptible individual. Because GC is remarkably breed specific, we suspect it is due to a heritable anomaly in Boxer dogs conferring susceptibility to intestinal invasion and persistence of E.coli. By comparing DNA profiles from Boxers with GC and controls we have identified a region of the genome that contains single nucleotide polymorphisms that are significantly associated with GC. This region is rich in genes and contains multiple candidate genes linked to IBD in people and murine models of IBD. Parallel investigations in French bulldogs with GC have revealed invasive E.coli and antibiotic responses similar to Boxer dogs. We speculate these breeds may share a common heritable defect. Further study is required to identify the specific genes related to GC in Boxers and French Bulldogs. It is our hope that these findings will lead to the development of genetic and functional tests to help eliminate this severe and increasingly antibiotic resistant form of colitis from the Boxer and French bulldog breeds.

Publication(s)

Manchester, A. C., Dogan, B., Guo, Y., & Simpson, K. W. (2020). Escherichia coli-associated granulomatous colitis in dogs treated according to antimicrobial susceptibility profiling. Journal of Veterinary Internal Medicine. https://doi.org/10.1111/jvim.15995

Dogan, B., Zhang, S., Kalla, S. E., Dogan, E. I., Guo, C., Ang, C. R., & Simpson, K. W. (2020). Molecular and Phenotypic Characterization of Escherichia coli Associated with Granulomatous Colitis of Boxer Dogs. Antibiotics, 9(9), 540. https://doi.org/10.3390/antibiotics9090540

Hayward, J. J., Castelhano, M. G., Oliveira, K. C., Corey, E., Balkman, C., Baxter, T. L., … Boyko, A. R. (2016). Complex disease and phenotype mapping in the domestic dog. Nature Communications, 7(1). https://doi.org/10.1038/ncomms10460