03143: Causative Role of Xenobiotic Exposures in Canine Gallbladder Mucocele Formation
Grant Status: Open
One Health: Yes
Mucocele formation is the most common gallbladder disease to afflict dogs. Despite the best surgical care, 17% will not survive. Retrospective studies alone report numbers of affected dogs in the thousands and over 80 publications have now addressed this specific disease. We don’t know what causes mucocele formation and have no way to predict, prevent, or reverse the epidemic rise in suffering and lost lives of these dogs. The long-range goal of our research is to identify the cause of mucocele formation in dogs. The objective of this study is to investigate a specific xenobiotic exposure that we identified in dogs with mucocele formation, for its potential to be the underlying cause of this disease. The hypothesis is that the discovered compound will be sufficient to inhibit fluid secretion and promote abnormal mucus formation by canine gallbladder epithelial cells; mechanisms that are consistent with an ability to promote mucocele formation in dogs. To test this hypothesis, investigators developed methods for culture of 3D “mini-gallbladder” organoids from a single canine gallbladder for use as a model for studying mucocele formation. This proposal aims are to determine if the discovered compound is sufficient to inhibit fluid secretion and/or promote accumulation of abnormal mucus secretions by canine gallbladder organoids. If the discovered compound mediates these mucocele-promoting effects, these studies will have identified the most probable cause of mucocele formation in dogs. This outcome is expected to have a significant impact on a prevalent problem by enabling veterinarians to prevent and treat this disease.
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