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Summary of Presentation at the Tibetan Terrier World Congress
Sturbridge, MA September, 2003
Martin Katz, Ph.D, University of Missouri, College of Veterinary Pathology

The Ceroid-Lipofuscinoses (CLs) are a group of inherited diseases that occur in a number of species of mammals, including humans, sheep, cattle, and dogs. CL has been reported in several dog breeds, including English Setters, Australian Shepherds, Polish Sheepdogs, and Tibetan Terriers. The name of the disease comes from the terms ceroid and lipofuscin, which were coined many years ago to describe pigments that accumulate in some cells during normal aging and more rapidly in some pathological conditions. A characteristic feature of the ceroid and lipofuscin pigments is that when they are examined in a microscope with ultraviolet or blue light, they give off a golden yellow color due to fluorescence. The presence of large amounts of this fluorescent pigment in a variety of cell types is a characteristic feature of all of the CLs, and is what separates them from other inherited disorders.

Another feature shared by the CL diseases is that they all involve degeneration of nervous tissue, primarily the brain and retina. It is this degeneration that is primarily responsible for the symptoms we see in these disorders. In Tibetan Terriers, symptoms of CL are usually first observed between 4 and 6 years of age. The symptoms become progressively worse and affected animals typically have to be euthanized by about 10 years old. The most commonly reported symptoms include: increased nervousness, loss of coordination, upset by loud or unfamiliar sounds, bumping into objects or barriers, impaired ability to go up or down stairs, decreased ability to see in dim light, loss of training, become aggressive, changes in eating habits, and seizures.

CL in Tibetan Terriers is inherited as an autosomal recessive trait. What this means is that at least one of the two copies of the CL gene has to be abnormal in each parent in order for a dog to be either affected or a carrier of the disease gene. It also means that in a breeding population, the disease can appear to be sporadic, often skipping one or more generations. Because of the late onset of behavioral signs and recessive nature of the disorder, it will be almost impossible to eradicate CL from the Tibetan Terrier breed based on selective breeding that relies on identifying affected dogs based only on disease symptoms.

The most reliable method for eliminating CL from Tibetan Terriers will be to identify the genetic (DNA) defect or mutation that is responsible for the disorder. An assay could then be developed to detect whether this mutation is present in each dog. The assay would be able to distinguish carrier from affected animals. We have initiated studies to develop such an assay. In humans, there are seven genes known to contain mutations that cause different forms of CL (the CLN genes). It is likely that CL in Tibetan Terriers results from a mutation in the canine version of one of these seven genes. We plan to analyze each of these genes in Tibetan Terriers with CL and in Tibetan Terriers that we know did not have CL. Any differences between affected and unaffected dogs will be considered possible disease causing mutations. We will confirm that a mutation causes Tibetan Terrier CL by analyzing DNA samples from a large number of affected and unaffected dogs. Once we have identified the disease causing mutation, we will develop an assay based on this mutation to distinguish between affected, carrier, and “normal” dogs. We will be able to perform the assay on DNA extracted from blood samples sent to our laboratory. In this way, we hope to help prevent CL from developing in future generations of Tibetan Terriers.