A team of researchers led by Ian Duncan, professor of neuroscience at the University of Wisconsin School of Veterinary Medicine, reported last November in the journal glia that they have found the genetic basis for canine tremor disorder. Their findings hold implications for dog owners, dog breeders, and families of individuals with certain disorders.
Canine tremor disorder is autosomal recessive, which means that both parents of a dog must be carriers for the dog to show tremors. The syndrome is characterized by tremors that grow in intensity for several weeks after some Weimaraner and Chow puppies are born. While only a small number of pups are affected by canine tremor disorder, and the trembling diminishes and stops in most cases, research shows that it persists longer in Chows than in Weimaraners for reasons still unknown, says Duncan.
Researchers have long known that canine tremor syndrome is caused by a unique, tract-specific disruption in the myelination in the spinal cord during canine development. But studies have not managed to find the genetic basis for the canine tremor disorder which is sometimes called “shaky puppy syndrome.”
A lack of myelin, a fatty substance that protects nerve fibers, disrupts electrical signals which are ultimately responsible for movement. The unique hypomyelination of the spinal cord giving rise to tremors was the hallmark that Duncan and other researchers studied to direct their search for the genetic basis of the disorder.
“A gene is involved here,” Duncan said. “This gene is involved in instructing the cell to make myelin in these areas in early development,” so it is natural to extend research to locate this gene and the mutation which leads to canine tremor disorder.
Unlike animal models like the jimpy mouse and myelin deficient rat, which have a human analog in Pelizaeus-Merzbacher disease, canine tremor disorder has no known human analog. This is unfortunate, as animal models often aid symptom identification, prognosis and treatment planning of their human counterparts.
However, there are a “number of descriptions of development disorders in children with delayed myelination,” Duncan said. Because canine tremor disorder is potentially a new disorder, it might have a human analog. Greater knowledge of this could help humans diagnose and treat human disorders based on the same genetic mutation.
Duncan and his team were able to isolate a mutation in the gene encoding the FNIP2 protein leading to the myelin defects in Weimaraner puppies.
Duncan and his team studied samples from unrelated pedigrees and a control group unaffected by the disorder using a genome-wide association (GWA) analysis. This analysis is the “gold standard” in this type of research with small samples, says Duncan. It identifies gene mutations using localization by examining genetic variants in a group of animals to see if any are associated with specific traits.
Isolating a single canine chromosome using GWA was not enough to determine the genetic basis of canine tremor disorder; the researchers needed to locate a specific gene and gene mutation.
Gene sequencing was performed and revealed a deleted nucleotide in a gene encoding FNIP2. In dogs with canine tremor disorder, the mutation causes FNIP2 to be shorter than in normal dogs. This results in the hypomyelination found in Weimaraners.
The process of myelination is not yet fully understood. In addition, the study notes that the function of FNIP2 in the myelination process is also not fully understood, and the long term effects of hypomyelination are still unknown.
However, this research makes great strides.
In addition to identifying the genetic basis for canine tremor disorder, researchers developed a DNA test for hypomyelination to assist owners and breeders in identifying affected and carrier dogs. The test is simple—breeders or owners submit a blood sample or mouth swab. DNA is isolated and sent to a genetics test lab at UC Davis, a research affiliate.
Breeders are able to use test results to select mating pairs to avoid producing affected dogs. Also, the genotype of more dogs with the syndrome can be determined for future research.
“People with these dogs will be told that tender loving care will get their dogs through this …and they will have a normal dog.” What is most important about this study is that it “recognized, identified and defined” the genetic basis for canine tremor disorder, Duncan said.
We know now from animal studies that there is recovery with time; thus, a child with a similar disorder may also improve with time. There is hope for these families, commented Duncan.
