Cystic fibrosis (CF) is a genetic disorder in humans that primarily affects the lungs and digestive system due to the production of thick, sticky mucus. Understanding mucus production in CF can help us better understand similar conditions in other parts of the body, such as the gallbladder. In dogs, a gallbladder mucocele happens when thick, dehydrated mucus builds up, leading to blockages or even rupture of the gallbladder. This condition is more common in certain purebred dogs, particularly Shetland Sheepdogs in the United States and Border Terriers in the United Kingdom.
How Can Research About a Rare Dog Gallbladder Condition Help with The Lungs of Humans?
Dr. Jody Gookin, the author of new research, says the disease has really only been seen in the last 20 years, and in a handful of breeds. Dr. Gookin is a professor of small animal internal medicine at North Carolina State University. She said that what was unique about the disease was how similar the studied gallbladders looked to those in animal models of cystic fibrosis.
In humans, the thick mucus that is associated with CF and causes tremendous damage and difficulty with lung function comes from a genetic defect called CFTR (Cystic Fibrosis Transmembrane Conductance Regulator). In a nutshell, CFTR is responsible for channels in epithelial cells that give off water and chloride. This lubricates cells and lets mucus flow freely. In cystic fibrosis, where there is a CFTR defect, the mucus just dehydrates and clogs the lungs. Unlike in human patients, though, it’s not the gallbladder that is clogged, as it is in dogs.
Dr. Gookin said there are no recorded cases of CF in non-human species. But when researchers look at CF in animals by purposely taking out the CFTR gene, the animals end up with the same gallbladder pathology that dogs with mucocele formation have. That observation is what made them wonder if dogs who had mucoceles had a CFTR mutation too–but they didn’t. They simply had a failure of the CFTR to function altogether .
The team looked at blood and genomes from eight Shetland sheepdogs with gallbladder mucocele formation. They looked at CFTR frequency variants in 115 dogs from12 breeds who were at high risk for mucocele formation. They also looked at over 2,500 dogs from 340 breeds not-at or at low-risk of the condition. They didn’t find any significant differences. The dogs with mucocele formation didn’t have mutations in CFTR like humans with CF do.
Dr. Gookin said that meant that the dogs who were starting to develop a dysfunction of their CFTR channel wasn’t due to a genetic defect. Instead, it could be from other genes or even environmental factors that influenced CFTR functions. To know more, the team will look at the entire genomes of the dogs to see what other mutations may exist and what might make dogs susceptible to the disease.
Dr. Gookan said that the big takeaway was the possibility of developing a CF-like disease that wasn’t caused by the CFTR mutation. This makes it super important to find the cause of CFTR mutations in dogs with mucoceles. It matters for both dogs and humans. It could help develop new treatment targets for both species, which could be incredible news for all who love those affected.
