The same gene mutation found in Tibetan Terrier dogs can also be found in a fatal human neurological disorder related to Parkinson’s disease.
Both humans and animals could benefit from the discovery, say a team of University of Missouri researchers who published the findings in the June 2011 issue of Neurobiology of Disease.
The disease in Tibetian Terriers is called adult-onset neuronal ceroid-lipofuscinosis (NCL). Within the dogs’ cells in the brain and eye, material that should be “recycled” builds up and interferes with nerve cell function. The buildup causes signs of dementia, impaired visual behavior and loss of coordination in dogs, beginning at around the age of five. The dogs also exhibit unwarranted aggression.
While there are many forms of NCL in humans, the symptoms of are similar in people and dogs. The disease is ultimately fatal for both. The canine genome map and DNA samples from dogs diagnosed with NCL allowed the researchers to pinpoint the specific gene that causes the disease.
The mutation, discovered by Fabiana Farias, doctoral candidate in the Genetics Area Program at the University of Missouri, as part of her thesis research, causes a hereditary form of Parkinson’s disease in humans. This suggests that the recycling that goes awry in NCL may also be involved in degenerative diseases like Parkinson’s.
Now, DNA from dogs can be tested to identify the presence of the mutated gene, and that test can ensure that Tibetan Terrier breeders do not pass it on to the next generation. The researchers also believe that they may be able to test potential human therapies on the animal population because they can use the DNA test to identify affected dogs before they start to show symptoms.
“Looking through samples collected from hundreds of dogs over many years, we got to the point where we’re able to say this is a disease caused by the mutation of one gene,” said researcher Martin Katz, professor of veterinary pathobiology. “Finding that gene was like finding a single house in a very large city – but we had the dog family history and the tools to look through the city in a systematic way to locate address of the mutation responsible for the disease.”
NCL ultimately took the life of Topper, a Tibetian Terrier owned by Lynn Steinhaus of Columbia. Steinhaus said Topper showed increased shyness around age five, and showed a loss of muscle control later. Topper also suffered seizures before he was euthanized in July of 2009. Topper’s DNA was used to further the study.
“This is really hard disease for dog owners to go through,” Steinhaus said. “Those seizures are just terrible.”
Along with Katz, the research team included Gary Johnson, associate professor of veterinary pathobiology; Dennis O’Brien, a professor in the Department of Veterinary Medicine and Surgery; and researchers from MU’s College of Veterinary Medicine; College of Agriculture, Food and Natural Resources; and the Mason Eye Institute.
The publication is the result of almost 10 years of work. The researchers believe it couldn’t have occurred without the unique combination of animal and human medical science at MU.
“Dogs and people suffer from the same diseases, and it’s much easier to discover gene issues in dogs because of the unique genetics of purebred dogs,” O’Brien said. “Because we have a medical school and veterinary school near each other, we can find the genes in the dog and then find out if they cause a similar disease in people.”