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Decoding man’s best friend

  • A brown and white bulldog looks at the camera with its tongue out. It stands in a green field.

    Decoding man’s best friend

    Genetic data brings CVM researchers closer to targeted treatments for urinary stones in dogs—and humans.
     

    Photo by David Gavi on Unsplash

Over the past 30,000 or so years, humans have played the role of geneticists, shaping domesticated wolves into nannies, hunting tools, and teacup-sized companions. Dogs have long been a part of the human family and today, scientists can unravel thousands of years of strategically molded DNA to pinpoint the source of disease. Recently, a team of researchers at the University of Minnesota College of Veterinary Medicine (CVM) has done just that. 

At the Minnesota Urolith Center, Eva Furrow, VMD, PhD, DACVIM, an associate professor of small animal medicine in the Department of Veterinary Clinical Sciences at the CVM, and collaborators have discovered a genetic mutation in dogs that could benefit urinary stone management in both humans and their best friends. Armed with this knowledge, veterinarians will be better equipped to prevent urinary stones and save dogs from needing surgery later on. 

Dr. Furrow with some miniature schnauzers she treated in a clinical study on ureter stones.
Furrow with Miniature Schnauzers that participated in genetic studies on urinary stones.

Crystals formed by minerals in the bladder, kidney, or urinary tract can clump together and grow to create urinary stones, which are too large to pass. The deposits are a familiar occurrence in any veterinarian’s office. One of the most common stone types is composed of calcium oxalate. While calcium oxalate stones are common in dogs in general, some breeds, such as Bichons or Schnauzers, are at particularly high risk. On the other hand, German Shepherds, Labrador Retrievers, and Collies rarely experience the condition. According to Furrow, scientists still do not understand why. But her team suspects it has to do with genetics. 

“Breeds are like one big extended family, so when you see something happening in one breed but not another, that points to an inherited predisposition,” says Furrow. She has worked for more than a decade to isolate genetic risk factors associated with urinary stones in dogs, pouring through thousands of stone submissions to the Minnesota Urolith Center and genetic data submissions to the CVM Canine Genetics Lab. Hidden in the data were clues veterinarians could use to design targeted treatments for urinary stones.

Breeds are like one big extended family, so when you see something happening in one breed but not another, that points to an inherited predisposition.

Eva Furrow, VMD, PhD, DACVIM

The path to targeted treatment

In the best cases, urinary stones cause irritation and accidents in the house. However, urinary stones can become a more serious issue. “When bladder stones pass into the urethra and get stuck, the dog can’t pass urine at all, which becomes a life-threatening emergency,” says Furrow. “You can’t dissolve calcium oxalate stones so they have to be removed, which for most dogs means major surgery.” And because some stones are small, surgeons often cannot remove all of the dangerous particles. The ones left behind can cause problems down the line. Even when all stones are successfully removed, one in two dogs who undergo this procedure has more stones develop within the next couple of years.

While most urinary stones appear in middle-aged dogs, Furrow noticed a pattern in the data bucking this trend—bulldogs were developing the condition much younger, often before their first birthday. “We knew there must be a stronger genetic risk factor in this breed, something that’s harder to overcome if bulldogs specifically were getting urinary stones so young,” she says.

Ureter stones from a dog
Bladder stones removed from a dog.

Her team identified a genetic mutation that causes this hereditary stone condition –– Hereditary Calcium Oxalate Urolithiasis, Type 1 (Hereditary CaOx1). The mutation happens to a gene that encodes a urinary protein that, when functioning normally, inhibits urinary stone formation. The abnormal protein has been found in bulldogs and seven other breeds of dogs who develop urinary stones at a young age, and the team continues to identify additional breeds who may be at high risk. 

“The protein is abnormally formed, but it isn’t missing,” says Furrow. “We are still in the early stages of understanding this mutation, but based on studies conducted on humans, we know there is potential to modify this protein in the urine.”

Since this particular protein blocks crystals — the basis of stones — from forming, some medical interventions may focus on helping the mutated gene better do its job.

Currently, veterinarians do not have a way to determine which urinary stone medications will be effective in which dogs, leaving them to guess which one to try first. With a better understanding of the root issue, Furrow’s team can develop targeted care plans for individual dogs. 

“Rather than trying six different treatments on a dog, or deciding which of the six to try at random, we can better select the best treatment for each animal by better understanding genetic factors,” says Furrow. 

Rather than trying six different treatments on a dog, or deciding which of the six to try at random, we can better select the best treatment for each animal by better understanding genetic factors. 

Eva Furrow, VMD, PhD, DACVIM

Healing together

Roughly 10 percent of people will develop kidney stones in their lifetime, and according to Furrow, a person’s family history best predicts whether or not they will suffer from urinary stones. The genetic mutation her team discovered in dogs is in the most abundant urinary protein found in both dogs and humans. Next, they’ll apply for grant funding to investigate the mutation itself. 

“By teasing apart what the mutant protein does in dog urine, we will pinpoint the problematic behavior that results in stones. Then, we can look at human urine to determine if this same abnormal behavior occurs and thus if similar treatments could be applied to human health,” says Furrow. “It’s a happy coincidence that what is beneficial for dogs’ health happens to also be relevant to humans.” 
 

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