Mucosal protection of the gallbladder is vital yet we know very little about the mechanisms involved. In domestic dogs, an emergent syndrome referred to as gallbladder
mucocele formation is characterized by excessive secretion of abnormal mucus that results in obstruction and
rupture of the gallbladder. The cause of gallbladder
mucocele formation is unknown. In these first mechanistic studies of this disease, we investigated normal and
mucocele-forming dog gallbladders to determine the source, identity, biophysical properties, and
protein associates of the culprit
mucins with aim to identify causes for abnormal mucus behavior. We established that
mucocele formation involves an adoptive excess secretion of gel forming
mucins with abnormal properties by the gallbladder epithelium. The mucus is characterized by a disproportionally significant increase in Muc5ac relative to Muc5b, defective
mucin un-packaging, and
mucin-interacting innate defense
proteins that are capable of dramatically altering the physical and functional properties of mucus. These findings provide an explanation for abnormal mucus behavior and based on similarity to mucus observed in the airways of people with
cystic fibrosis, suggest that abnormal mechanisms for maintenance of gallbladder epithelial hydration may be an instigating factor for
mucocele formation in dogs.