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A recent study has uncovered a canine gallbladder condition characterized by an abnormal buildup of mucus, similar to the symptoms seen in human cystic fibrosis (CF) patients. This disease, linked to improper gene expression associated with CF in humans, raises potential implications for both canine health and understanding of human CF.
The condition known as gallbladder mucocele formation occurs when thick, dehydrated mucus accumulates in the gallbladder, disrupting its normal function and potentially resulting in obstruction or rupture. This affliction predominantly affects purebred dogs; in the United States, Shetland sheepdogs are most frequently diagnosed, while in the United Kingdom, border terriers are the primary victims.
Dr. Jody Gookin, a professor of small animal internal medicine at North Carolina State University and the lead author of the study, notes, “The emergence of this disease has only been recognized over the past two decades among certain breeds. What piqued my interest was the visual similarity of these gallbladders to those found in animal models of CF.”
In humans, the thick mucus attributed to CF is due to a genetic defect in the CFTR gene, which is essential for creating channels in epithelial cells responsible for secreting chloride and water. These channels serve to hydrate the mucus, preventing it from becoming too thick and consequently clogging critical areas such as the lungs and intestines. However, it is noteworthy that human gallbladders do not fill with dehydrated mucus as those of affected dogs do.
“There have been no documented cases of naturally occurring CF in any non-human species,” Gookin explains. “However, studies on CF in animals that have had the CFTR gene knocked out often reflect the gallbladder pathology we observe in canines with mucocele formation. This raised the question of whether dogs with mucoceles carried a mutation in CFTR, but that was not the case. Instead, they exhibit a dysfunction in the CFTR gene’s functioning.”
To investigate, Gookin conducted whole genome sequencing on blood samples from eight Shetland sheepdogs diagnosed with gallbladder mucocele formation. She compared the variants discovered in the CFTR gene among these dogs to those from 115 dogs from breeds known to have a higher risk for this disease and 2,519 dogs from breeds considered lower risk. The analysis showed no significant differences in the CFTR gene among the groups, nor did the affected dogs present mutations in areas of the CFTR gene known to impact humans with CF.
“This suggests that some underlying factor is causing the CFTR channel dysfunction in these dogs that isn’t related to a mutation in the gene itself,” Gookin states. “Other genetic or environmental influences could be responsible for the altered functioning of the CFTR. Our future research will focus on analyzing the complete genome of these dogs to explore other mutations that might contribute to their susceptibility to this disease.”
“One of the most fascinating insights from this study is the possibility of developing a CF-like condition without a direct mutation in the CFTR gene,” she adds. “Unraveling the root cause of CFTR dysfunction in dogs with mucocele formation could provide crucial knowledge for humans, where similar underlying issues could contribute to CF-like diseases or identify new treatment avenues for CF.”
The findings of this study are published in the journal Gastrointestinal and Liver Physiology, with funding provided by the Morris Animal Foundation and the National Institutes of Health. The research also involved contributions from various individuals at North Carolina State University and other academic institutions.
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