A Newly Discovered Mutation May Explain Why Some Dogs Can't Breathe Well

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

As wonderfully cute as dog breeds like the French Bulldog look (for some people at least), it’s long been thought that these dogs’ distinctively compact skulls also make them very vulnerable to severe health and breathing issues. But new research out of Europe suggests that smushy faces are only part of the problem for some breeds—an unrelated genetic mutation that’s also found in dogs without these skulls may be partly to blame too.

French bulldogs and similarly squished-head dogs, such as the pug, are known as brachycephalic dogs. Compared to dogs like the labrador, these pups are bred to have incredibly flat noses and foreheads. Their compact skull, however, can oftentimes result in body parts like the palate (the soft part of the roof of the mouth) or nostrils being too big or small. When that happens, airflow can be obstructed and cause chronic breathing problems. The catch-all term for this phenomenon is called brachycephalic obstructive airway syndrome, or BOAS.

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Senior study author Jeffrey Schoenebeck, a dog geneticist at the University of Edinburgh’s Royal School of Veterinary Studies, has long studied and tried to better understand BOAS in brachycephalic dogs. But years ago, he began hearing stories from breeders of the Norwich Terrier, a UK-originated dog once bred to catch rodents. Their dogs were coming down with symptoms remarkably similar to BOAS. While Norwich Terriers are definitely as small as a pug or Frenchie, though, they’re not brachycephalic.

“That made us wonder if there was something similar shared across these different breeds, or if we were seeing two different diseases that just looked very similar,” Schoenebeck told Gizmodo over the phone.

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

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

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“This discovery changes how we view respiratory disease predisposition in the dog, offers potential genetic screens and highlights a new biological function for ADAMTS3,” the authors wrote.

The ADAMTS3 gene, found in the 13th chromosome, is thought to help in the development of the lymphatic system, the network of vessels and organs that ferry white blood cells and waste throughout the body as needed. Other mutations in ADAMTS3, in both dogs and humans, have previously been linked to facial deformities and lymphatic vessel blockages, which can cause a build-up of fluid and swelling.

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That said, no single study can or should be used to prove thing A causes thing B. So Schoenebeck and his team plan to do follow-up research, possibly using dog cell-lines in the lab, to confirm their findings.

But anecdotally, Norwich Terrier breeders who turned to his co-authors in Switzerland for help have been able to reduce the likelihood of the syndrome appearing in their dogs over time, by identifying dogs that are more or less likely to develop the condition, based on their breathing tests. And when they compared more recent populations of these dogs to older ones, the newer dogs were less likely to carry the ADAMTS3 mutation.

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“In the 90s, something like 80 percent of the Norwich Terriers that came into their clinic had poor breathing and this mutation. But it’s decreasing further and further over time,” Schoenebeck said. “They didn’t know it at the time, but they were actually selecting against this thing that we think is causing this disease.”

But even if ADAMTS3 does exclusively cause the BOAS-like syndrome in Norwich Terriers, it’s a more complex picture for bulldogs.

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“If a French bulldog is conforming to the breed standard, then they all have a certain degree of risk, due to their skull shape. But there’s other things that could be contributing to that risk,” Schoenebeck said. “And this could be one of the things that may be segregating them into different levels of risk. But to what degree, we don’t just know yet.”

Because of that, there needs to be more research looking directly at the link between ADAMTS3 and BOAS in bulldogs. These would include studies where a bulldog’s symptoms is measured against the amount of bad ADAMTS3 copies, similar to what was done in this study.

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There might also come a time when ADAMTS3 could be used to guide the treatment of bulldogs with BOAS, Schoenebeck added. Bulldogs with especially bad BOAS often get corrective surgery to help them breathe easier. But we know already that fluid build-up in a dog’s airways with BOAS is linked to worse recovery afterward. So if a dog’s BOAS is directly linked to this mutation, that could mean they won’t respond as well as to the treatment.

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About the author

Ed Cara

Science writer at Gizmodo and pug aficionado elsewhere