By looking at him, you might not know Thabiso had two ruptured cruciate ligaments. “He was a massive dog, 125 pounds,” Allison Smith says about her beloved Labrador Retriever.
When Smith got Thabiso in 2010, he was three and a half years old with a slight limp. Smith didn’t think much of it until a visit to the veterinarian revealed Thabiso had two ruptured cruciate ligaments, which serve as a primary stabilizer in a dog’s knee. Thabiso’s knees had been injured so long that he had “learned to cope” with the pain, Smith says.
Thabiso isn’t alone. Cruciate ligament ruptures are one of the biggest health problems in the veterinary medical field of canine orthopedics.
However, there is now a way to help prevent this disabling disease through genetic testing. Researchers in the Comparative Genetics and Orthopaedic Research Laboratory at the University of Wisconsin–Madison School of Veterinary Medicine have found a way to determine whether a dog is susceptible to the condition. The screening test, the first of its kind in companion animals, requires only a cheek swab that can be collected at home or a small blood sample.
The researchers made the screening test available for Labrador Retrievers, the most popular dog breed in America, in September. The Labrador breed has a high risk of developing the disease; five to 10 percent of Labradors rupture a cruciate ligament within their lifetime.
The research team is now working to extend the development of predictive genetic testing to other breeds with a high risk of cruciate rupture, like the Rottweiler and Newfoundland.
Researchers at the University of Wisconsin–Madison School of Veterinary Medicine have found a way to determine whether a dog is susceptible to cruciate ligament rupture. The screening test, the first of its kind in companion animals, requires only a cheek swab that can be collected at home or a small blood sample.
The canine cranial cruciate ligament is much like a human’s anterior cruciate ligament (ACL), acting as an important stabilizer of the knee joint in both species. Although any dog can rupture the ligament, it is uncommon to happen through injury alone. Rather, genetics play an essential role in the degeneration of the cruciate ligament, increasing the risk of a rupture.
“In dogs, ligament degeneration and progressive rupture of collagen fibers in the ligament tissue leads to the development of knee joint instability over time,” says Peter Muir, laboratory co-director and a professor in the Department of Surgical Sciences in the UW School of Veterinary Medicine.
Both genetic and environmental factors, such as physical health, body condition and neutering, contribute to chronic ligament degeneration.
Pinpointing whether a dog is more likely to rupture a cruciate ligament due to genetics allows the dog’s owner and veterinarian to take preventative measures, such as keeping the dog physically healthy and monitoring for signs of emerging injury. It can also help avoid the expenses and recovery involved in a rupture.
Rupturing a cruciate ligament, either partially or entirely, is a lengthy, expensive process for dogs and their people. Surgical treatment can cost between $4,000-$7,000 per knee in a dog. And once a rupture happens in one knee, there’s a 50 percent chance the other will tear as well.
This was the case for Thabiso. He had two different surgeries, one in 2011 and another in 2014. Although the procedures helped him walk more comfortably and return to an active life, recovery took months, and lifelong knee arthritis was inevitable.
Creating a genetic test for this disease was a long process. Muir, School of Veterinary Medicine assistant professor Susannah Sample and other lab members spent years screening for the disease. They examined the genotype, or genetic makeup, of over 1,000 Labrador Retrievers across the country. Thabiso was one of these dogs, joining the study in 2016.
Muir explains that genetic markers for cruciate ligament ruptures are more complex than markers for other traits. Most genetic tests look for one specific DNA mutation to determine whether a particular disease or trait is present. However, cruciate ligament rupture results from multiple gene variations throughout the dog’s genome.
“There are all these little variants that act together,” Muir says, “So, any individual Labrador that inherits enough small effect variants in combination will have high genetic risk typical of a cruciate ligament rupture case.”
Researchers used a method called array genotyping to determine genetic markers for each dog. By analyzing the DNA and gene variants in multiple samples, they could identify the small variants associated with cruciate ligament rupture.
These findings allowed scientists to determine the genetic risk of developing cruciate ligament rupture in Labrador Retrievers. They found a heritability estimate of 0.62, meaning for each individual Labrador that develops cruciate ligament rupture, about 62 percent of the risk is genetic, and approximately 38 percent is environmental. From this research, the lab can now test individual Labrador Retrievers for the genetic risk of a cruciate ligament rupture with 98 percent accuracy.
Pinpointing whether a dog is more likely to rupture a cruciate ligament due to genetics allows the dog’s owner and veterinarian to take preventative measures, such as keeping the dog physically healthy and monitoring for signs of emerging injury. It will also help breeders reduce the incidence of this disabling disease in the Labrador Retriever population over time and improve the breed’s genetic health.
Researchers determined Thabiso’s tears were from genetic rather than environmental factors. Although he has since passed away, the test will allow future pet owners to prevent this disabling disease. It will also help breeders reduce the condition’s incidence in the Labrador Retriever population over time and improve the breed’s genetic health.
These efforts not only benefit dogs, according to Muir, but further genetic testing research for animals and humans alike.
“Our initial interest in the disease is as a spontaneous animal model for human orthopedic disease,” he explains, to better understand human ACL tears and associated genetics.
If you want to learn whether your Labrador Retriever is at high risk for developing a cruciate ligament tear, contact the Comparative Genetics and Orthopaedic Laboratory at firstname.lastname@example.org. Testing costs $250 and will take four to six weeks for results.
Graduate Research Training
Comparative Genetics and Orthopaedic Research Laboratory co-directors Peter Muir and Susannah Sample MS’07, DVM’09, PhD’11 are trainers in the school’s Comparative Biomedical Sciences (CBMS) graduate program and mentor several CBMS students in their lab, including Alexander Chu, Jackie Perino, and Ryan Anderson. Alumnae Lauren Baker MS ’14, DVM’16, PhD’19 and Emily Binversie MS’16, DVM’18, PhD’21 also contributed greatly to understanding the genetic basis of canine cruciate ligament rupture as members of the lab during their graduate studies. And Mehdi Momen, a postdoctoral scientist in the lab, has been pivotal in the development of this test.
Binversie, a member of the lab as a doctoral student, received the 2022 basic sciences research manuscript award from the Society of Phi Zeta, the international honor society of veterinary medicine. The group recognizes and promotes scholarship and research related to the welfare and diseases of animals.
Binversie’s winning paper, published in the scientific journal PLOS One, examined the genetic origin of cranial cruciate ligament rupture in dogs. Binversie is now completing a residency in dermatology at Iowa State University’s College of Veterinary Medicine.