Department of Clinical Sciences
Email: email@example.com; Phone: 607-253-3251
Sponsor: American Kennel Club (AKC) Canine Health Foundation (CHF)
Grant Number: 23405
Title: Granulomatous Colitis in Boxer Dogs and French Bulldogs: Mapping of Disease Associated Loci and Functional Analysis of Bacterial Killing
Project Amount: $187,730
Project Period: 01/01/14-12/31/15
DESCRIPTION (Provided by Applicant): Granulomatous colitis (GC) is a severe inflammatory bowel disease (IBD), usually diagnosed in young Boxer dogs and French Bulldogs. Affected dogs present with hemorrhagic diarrhea, often progressing to weight loss and debilitation. Recent studies have identified invasive Escherichia coli within macrophages in the inflamed large intestine, and eradication of E.coli induces dramatic clinical and histologic improvement. Unfortunately, the emergence of antimicrobial resistance has greatly reduced our ability to treat this disease, and persistently affected dogs are frequently euthanased. The type of E.coli isolated from Boxers with GC is very similar to adherent and invasive E coli (AIEC) associated with IBD in people. This type of E.coli are considered opportunistic pathogens that can exploit genetic defects in bacterial killing in an IBD susceptible individual. Because GC in dogs is remarkably breed specific we suspect it is due to a heritable abnormality in Boxer dogs and French Bulldogs that confers susceptibility to invasion and persistence of E.coli. In preliminary studies we have identified a region of the canine genome that is associated with GC in Boxers and French Bulldogs. This region contains candidate genes associated with IBD in people and murine models, and has been specifically linked to sensing and killing of E.coli. The purpose of this study is to identify the gene(s), causal varaint(s) and cellular pathways involved in the development of GC. This would enable the development of screening tests to eradicate this disease, and advance understanding of the development of IBD in dogs and people.