Researchers at several institutions in the United States and Sweden have found that a mutation in the gene for superoxide dismutase 1 (SOD1), known to cause ALS (amyotrophic lateral sclerosis) in 1 percent to 3 percent of human cases, also can cause an ALS-like disease in dogs.
These dogs are the first spontaneously occurring animal model of ALS discovered, the researchers say in their paper, published online Feb. 2 in Proceedings of the National Academy of Sciences.
The investigators, coordinated by Gary Johnson and Joan Coates at the University of Missouri in Columbia, analyzed DNA samples from 38 Pembroke Welsh corgi dogs with an ALS-like disease and 17 related, clinically normal dogs and found a mutation in the SOD1 gene that was significantly associated with the illness.
Unlike most human cases, however, this SOD1-related disease is recessive, not dominant, meaning an animal must have a mutation in both its two SOD1 genes in order to show symptoms. Humans generally only need one SOD1 mutation to show disease symptoms.
The investigators went on to identify a similar disease caused by the same SOD1 mutation in boxers, Rhodesian ridgebacks, German shepherds and Chesapeake Bay retrievers.
The dogs showed clinical signs of degenerating upper (brain) and lower (spinal cord) motor nerve cells (motor neurons), as in human ALS. When the dogs' spinal cords were examined microscopically, they revealed loss of nerve fibers and SOD1-containing clumps in their nerve cells, which are also seen in ALS patients.
Dogs may be better predictors of human responses to experimental ALS treatments than mice, because they're closer in size to humans than rodents are, their nervous systems are more similar to humans in structure and complexity, and they're unlikely to possess the very high levels of mutated SOD1 protein found in some mice but not in humans with the disease.