Researchers Find Cause of Muscle-Stiffness Disease (5/15/2007)

Imagine a dog running after a ball, only to stiffen up and fall over because of a genetic muscle cell disorder. It may sound almost comical, but this disorder, called Myotonia congenita, affects dogs, cats, horses, water buffalo, and even people.

Three University of Guelph professors have found the cause of the disease that temporarily prevents an animal's muscles from relaxing after they contract. The research by Andrew Bendall, Brad Hanna and Roberto Poma is published today in the Journal of Veterinary Internal Medicine .

In humans, so far more than 80 mutations of the skeletal muscle chloride channel gene (called CLCN1) – which temporarily prevents muscles from relaxing after they contract – have been found. In animals, scientists have barely begun to scratch the surface of finding the causes of the muscle disease. Bendall and Hanna of the Department of Molecular and Cellular Biology have discovered the mutation associated with Myotonia congenital in Australian Cattle Dogs and in a Maltese-cross dog.

"There are probably eight breeds of dogs known to have Myotonia, but up until our study, the Miniature Schnauzer was the only breed for which a specific genetic mutation had been found," says Bendall.

Adds Hanna: "I think there's a misunderstanding among some veterinary practitioners that once you find a mutation that causes the disease, that's it. The human example shows us clearly that, no, in different families there may be different mutations."

That means that even though a blood test has been established to detect Myotonia in the Miniature Schnauzer, it's unlikely that it will detect the disease in any other breed of dog. Because Bendall and Hanna found the mutation in the Australian Cattle Dog, they were able to develop a blood test to detect the disease in that breed which is now offered at the provincial diagnostic Animal Health Lab at U of G.

"We found that in the Australian Cattle Dog it's a truncation mutation, so there's actually a portion of the skeletal muscle chloride channel that's missing," says Hanna. "Eighty-eight amino acids are missing at one end of the channel."

Bendall and Hanna's research will not only benefit the owners of Australian Cattle Dogs, but "by identifying the kinds of mutations that affect the function of the protein, you can learn something about how the normal protein works," says Bendall.

The fact that Bendall and Hanna have successfully cloned the CLCN1 gene in the Australian Cattle Dog and found the mutation means that they are now able to find mutations in other breeds more quickly.

Since their success in Australian cattle dogs, they've also discovered the mutation in a Maltese-cross with a severe case of Myotonia. "We have found a missense mutation, which results in the substitution of one amino acid for another in the protein," says Hanna. "That amino acid has not been found to be mutated in this way in humans, so we're in the process of doing the functional work to determine the significance of this change."

When veterinarians diagnose Myotonia in animals, since there's no known treatment for the disease, they often don't refer clients to Bendall and Hanna for testing.

"We would be interested in hearing from veterinarians who have identified animals of any breed or any species with a similar disorder," says Hanna. "It's possible, especially with purebred animals, for this type of disease to become widely disseminated, so by developing blood tests we can help breeders eliminate these disorders."

Note: This story has been adapted from a news release issued by the University of Guelph

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