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North Carolina State University, July 2024 – Recent research has unveiled intriguing parallels between a gallbladder disease in dogs and human cystic fibrosis (CF), offering new insights into both conditions. The study, led by Dr. Jody Gookin, a professor of small animal internal medicine at North Carolina State University, explores how canine gallbladder mucocele formation could advance understanding of CF in humans.
Gallbladder mucocele formation, primarily observed in purebred dogs such as Shetland sheepdogs in the U.S. and border terriers in the U.K., involves the buildup of thick, dehydrated mucus. This mucus obstructs and eventually ruptures the gallbladder, mirroring the mucus buildup seen in CF patients. Despite the similarities, the disease in dogs is not caused by mutations in the CFTR gene, which is known to be defective in human CF patients.
CF in humans results from a defect in the CFTR gene, which normally helps maintain the fluidity of mucus by regulating chloride and water transport in epithelial cells. This defect leads to the accumulation of thick, sticky mucus that clogs the lungs and intestines. Although CFTR gene mutations are absent in dogs with mucocele formation, Dr. Gookin’s research reveals that the CFTR channel still fails to function properly in these animals.
Dr. Gookin and her team conducted whole genome sequencing on eight Shetland sheepdogs with gallbladder mucocele formation. They compared their genetic data with that of 115 dogs from high-risk breeds and 2,519 dogs from low-risk breeds, finding no significant genetic differences or CFTR mutations in the dogs with mucocele formation. This suggests that CFTR dysfunction in these dogs may be due to factors other than genetic mutations, such as environmental influences or interactions with other genes.
“The most eye-opening piece for me is the idea that it is possible to develop a CF-like disease that isn’t caused by a mutation in the CFTR gene,” Dr. Gookin said. “Identifying the underlying cause of CFTR dysfunction in dogs with mucocele formation has important implications for human CF patients, potentially revealing new treatment targets.”
The study’s findings, published in AJP Gastrointestinal and Liver Physiology, are supported by the Morris Animal Foundation and the National Institutes of Health. The research team includes Jenny Holmes, Stephen Stauffer, Nicole Torres-Machado, Bryanna Meredith, Michael Vandewege, Gabriela Seiler, Kyle Matthews, and Kathryn Meurs from NC State, as well as Steven Friedenberg from the University of Minnesota and Lane Clark from the University of Missouri.
This breakthrough underscores the potential of using canine models to gain insights into human diseases, highlighting how comparative studies across species can reveal novel pathways and therapeutic targets.
For more details, refer to the full study: Gookin, J. L., et al. (2024). Acquired dysfunction of CFTR underlies cystic fibrosis-like disease of the canine gallbladder. AJP Gastrointestinal and Liver Physiology. doi.org/10.1152/ajpgi.00145.2024.
