A newly discovered mutation may explain why some dogs can not breathe well



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A Norwich Terrier
Photo: Marcia A. Sessions (University of Edinburgh)

As wonderfully cute as dog breeds like the French Bulldog (for some people at least), it has long been thought that the particularly compact skulls of these dogs also make them very vulnerable to serious health and breathing problems. But new research from outside Europe suggests that bushy faces are only part of the problem of some breeds – an unrelated genetic mutation that also exists in dogs without these skulls can also be implicated.

French bulldogs and square-headed dogs, such as pugs, are known as brachycephalic dogs. Compared to dogs like Labrador, these puppies have an incredibly flat nose and forehead. However, their compact skull can often cause parts of the body such as the palate (the soft part of the roof of the mouth) or nostrils too big or too small. When this happens, the airflow can be clogged and cause chronic respiratory problems. The catch-all term for this phenomenon is called brachycephalic airway syndrome, or BOAS.

Jeffrey Schoenebeck, senior research author at the Royal School of Veterinary Studies at the University of Edinburgh, has been studying for a long time and is trying to better understand BOAS in brachycephalic dogs. But years ago, he began hearing stories from breeders of the Norwich Terrier, a dog of British origin who had been bred to catch rodents. Their dogs had symptoms remarkably similar to those of BOAS. The Norwich Terriers are certainly as small as a pug or a French, but they are not brachycephalic.

"This led us to wonder if there was something similar shared between these different breeds or if we were observing two different diseases that looked very similar," Schoenebeck told Gizmodo over the phone.

Finally, Schoenebeck and his team decided to coordinate their activities with other researchers, including some who have spent decades collecting DNA and examining the airways of hundreds of Norwich Terriers, to solve the mystery.

The results of their research, published Thursday in PLOS-Genetics, suggest that a specific mutation of a gene called ADAMTS3 can totally explain this syndrome in Norwich Terriers. Burrows with the worst symptoms and deformities of the tissues, for example, were usually dogs with two copies of the mutation, indicating a clear cause-and-effect relationship. But oddly, they also found this same mutation in the DNA of some English and French Bulldogs.

"This discovery changes our perception of the predisposition to respiratory diseases in dogs, offers potential genetic screens and highlights a new biological function for ADAMTS3," write the authors.

The ADAMTS3 gene, present in the 13th chromosome, is thought to contribute to the development of the lymphatic system, the network of vessels and organs that carry white blood cells and waste into the body, as needed. Other ADAMTS3 mutations, in dogs and humans, have previously been associated with facial malformations and obstructions of the lymphatic vessels, which can cause fluid accumulation and swelling.

That said, no study can or should be used to prove a thing as a cause B. Schoenebeck and his team plan to do follow-up research, possibly using dog cell lines in the laboratory, to confirm their findings. .

But, anecdotally, the Norwich Terrier breeders who used his co-authors in Switzerland were able to reduce the likelihood of the syndrome appearing in their dogs over time, by identifying more or less susceptible dogs to develop the disease their breathing tests. And when they compared the newer populations of these dogs to older dogs, the new dogs were less likely to carry the ADAMTS3 mutation.

"In the 1990s, about 80% of Norwich Terriers entering their clinic had bad breathing and this mutation. But this decreases more and more over time, "said Schoenebeck. "They did not know it at the time, but they were actually choosing something that we think is causing this disease."

However, even if ADAMTS3 exclusively causes BOAS syndrome in Norwich Terriers, the situation is more complex for bulldogs.

"If a French bulldog conforms to the standard of the breed, they all have some degree of risk because of the shape of their skull. But there are other factors that could contribute to this risk, "Schoenebeck said. "And that could be one of the things that could separate them into different levels of risk. But to what extent, we do not know yet. "

For this reason, more research is needed on the direct link between ADAMTS3 and BOAS among bulldogs. These would include studies where the symptoms of a bulldog are measured against the amount of defective ADAMTS3 copies, similar to that performed in this study.

There may also be a time when ADAMTS3 could be used to guide the treatment of bulldogs with BOAS, Schoenebeck added. Bulldogs whose BOAS is particularly bad often undergo corrective surgery to help them breathe better. But we already know that the accumulation of fluid in the respiratory tract of a dog with BOAS is linked to a worse recovery afterwards. So, if a dog's BOAS is directly related to this mutation, it could mean that it will not respond as well as treatment.

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