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Unraveling a genetic mystery

  • 8-week-old bulldog b=puppy

    Unraveling a genetic mystery

    Study participants sought to continue research into English bulldogs’ early urinary stone development

    An English bulldog named Harry, pictured as an 8-week-old puppy, lent a helping paw in research seeking to uncover the cause of urinary and bladder stones that form at a young age in his breed. Photo courtesy of Kelly Whitstone. 

The University of Minnesota Urolith Center (MUC) receives thousands of urinary and bladder stone samples each year and has amassed a treasure trove of data. The stones and their corresponding data can tell a story and sometimes that story is a mystery. 

Dogs that develop stones tend to form them around middle age, typically between 7 and 10 years old. One of the common stone types is calcium oxalate. Its development is hereditary but also can be influenced by other factors such as diet and age. 

The mystery begins when some dogs form calcium oxalate at a much younger age than usual, in some cases less than 2 years old. While reviewing data on dogs that developed stones in this young age group, researchers noticed a trend in English bulldogs. 

“We found that English Bulldogs were one of the top breeds forming these stones at a young age,” says Dr. Eva Furrow, co-director of the MUC and associate professor of small animal internal medicine and genetics at the UMN College of Veterinary Medicine. “This was a shock to us because English Bulldogs are not one of the most common breeds to form calcium oxalate stones overall. However, when they do form them, it often occurs when they are young adults or even still puppies. This is unusual and quite different from what we see in other breeds.”

Harry, an English bulldog whose genome played
an important role in research at the Minnesota
Urolith Center. Photo courtesy of Kelly Whitstone. 

The theory that a gene defect was the culprit behind the formation of the stones led MUC researchers to seek bulldogs who had developed stones at a young age for further study. One of them was Harry, a now 10-year-old bulldog owned by Kelly Whitstone, a former UMN Veterinary Diagnostic Lab employee.

“When Harry was around 4 years old, he was diagnosed with hip dysplasia and couldn’t go for long walks anymore,” Whitstone says. “At that time, they found crystals in his urine.” 

While crystals do not always indicate the presence of stones, they did in Harry’s case. Harry underwent surgery to remove bladder stones, which were identified as calcium oxalate. He adopted a special diet after his diagnosis and while he was found to have a recurrence of very small stones later on, he hasn’t required another surgery. Currently, Whitstone says Harry spends his days soaking up the afternoon sun and taking naps, but back in 2018 and 2019, his genes were hard at work for science.  

Harry joined two other bulldogs in the first stage of the calcium oxalate study, which sequenced their entire genomes in hopes of identifying a possible source of the early stone formation. Using that information, researchers made a discovery.

“We found that they had a mutation in a major urinary protein that is needed to prevent stone formation,” Furrow says. “Now, we are working on understanding how this mutation is changing the protein and whether we can correct the problem with medication or diet.”

As part of that continued work, the MUC has opened a study for English bulldogs with and without a history of calcium oxalate urinary stones. The study seeks to identify how urine from dogs affected by the specific genetic defect—officially called hereditary calcium oxalate urolithiasis, type 1 (CaOx1)—differs from unaffected dogs without urinary stones with the hope that this information will ultimately inform treatment recommendations for affected dogs.

The potential impact of this study reaches beyond veterinary medicine. Characterizing this mutation and its effects will also lead to novel therapies for people with calcium oxalate stones.

The study is enrolling neutered, male English bulldogs between 2–8 years of age. They cannot be receiving steroid or diuretic therapy, though most other medications are permitted. Participants cannot have a history of urinary stones or kidney disease, but most other medical conditions are permitted.

Participation in the study will require the collection of a urine and DNA sample. Owners are asked to collect their dog’s urine sample at home using a kit provided by MUC and returned via pre-paid mail or brought to Dr. Furrow. A DNA sample can be collected with a cheek swab kit at home or through a visit to the Lewis Small Animal Hospital for a blood draw.

Urinary analysis tests will be run at no charge and owners will receive free genetic testing results for the CaOx1 mutation, as well as for hereditary hyperuricosuria, a risk factor for urate stones. 

People with qualifying dogs and interested in participating in the study can contact Furrow and the UMN Canine Genetics Laboratory at

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