Emerging Disease in Dogs is Similar to Cystic Fibrosis in Humans

Emerging disease in dogs is similar to cystic fibrosis in humans. But what this disease is? A canine gallbladder disease marked by the accumulation of abnormal mucus is known as gallbladder mucocele formation, results from the slow buildup of thick, dehydrated mucus that disrupts normal gallbladder function, eventually causing obstruction and rupture. Mucocele formation primarily affects purebred dogs, being most common in Shetland sheepdogs in the U.S. and border terriers in the U.K.

Date	July 29, 2024
Source	North Carolina State University
Summary	A canine gallbladder disease characterized by the buildup of abnormal mucus, similar to that observed in human cystic fibrosis (CF) patients, is linked to improper expression of the CF-associated gene. This discovery may have significant implications for both human CF patients and animal models of the disease.

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What is Cystic Fibrosis Disease

In humans, the thick immobile mucus associated with CF results from a defect in the CFTR gene, which is responsible for creating channels in epithelial cells that secrete chloride and water, keeping mucus moist and moveable. In CF, the absence of these channels causes mucus to dehydrate and clog the lungs and intestines. However, in human CF patients, the gallbladders do not fill with dehydrated mucus.

There are no recorded instances of naturally occurring CF in any non-human species. But when researchers study CF in animal models by knocking out the CFTR gene, those animals often develop the same gallbladder pathology we see in dogs with mucocele formation. That led us to wonder whether dogs with mucoceles had a mutation in CFTR -but they didn’t. What they did have was a failure of CFTR to function.”

Video of Cystic Fibrosis

How Emerging Disease in Dogs is Similar to Cystic Fibrosis in Humans

Researchers conducted whole genome sequencing on blood from eight Shetland sheepdogs with gallbladder mucocele formation and compared the location and frequency of CFTR gene variants to 115 dogs from 12 breeds at high risk for mucocele formation and 2,519 dogs from 340 breeds considered low risk for mucocele formation.

There were no significant differences between the groups, and the dogs with mucocele formation did not have mutations in CFTR in locations where humans with CF do.

“This means that somehow these dogs are acquiring a dysfunction of the CFTR channel that is not based on a gene defect,” researchers explain. “It could be due to other genes and environmental factors influencing CFTR function. Our next steps will be examining the entire genome of these dogs to see if there are other mutations contributing to this disease.

The most eye-opening piece for me is the idea that it is possible to develop a CF-like disease not caused by a CFTR gene mutation. Identifying the cause of CFTR dysfunction in dogs with mucocele formation has important implications for human patients, where similar factors might contribute to CF-like diseases or reveal new treatment targets for CF.”

The research is published in Gastrointestinal and Liver Physiology and was supported by the Morris Animal Foundation and the National Institutes of Health.

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