Researchers find link between mutations in gene called RAB 24 and inherited neurodegenerative disease

North Carolina State UniversityFeb 7 2014

Researchers from North Carolina State University have found a link between a mutation in a gene called RAB 24 and an inherited neurodegenerative disease in Old English sheepdogs and Gordon setters. The findings may help further understanding of neurodegenerative diseases and identify new treatments for both canine and human sufferers.

Hereditary ataxias are an important group of inherited neurodegenerative diseases in people. This group of diseases is the third most common neurodegenerative movement disorder after Parkinson's and Huntington's diseases.

In people with hereditary ataxia, neurons in the cerebellum that control movement begin to die, causing a gradual loss of coordination. Hereditary ataxias are also recognized in certain breeds of dog, including the Old English sheepdog and the Gordon setter.

NC State neurologist Natasha Olby and a team of researchers from the National Institute on Aging and the Broad Institute of MIT and Harvard looked at 630 Old English sheepdogs and mapped ataxia genetically in the families of affected animals. Eventually they mapped the disease to a gene, RAB 24, located on chromosome 4. A mutation in RAB 24 was closely associated with development of the disease, and on screening of affected dogs of other breeds, the identical mutation was found in Gordon setters, providing additional evidence that this mutation is important.

"Rab 24 is a protein that is believed to be important to the process of autophagy - which is how cells cleanse themselves of waste," Olby says. "We know that autophagy and neurodegeneration are connected, so pinpointing this protein is important to our understanding of the disease process."

"We have not yet proven that this mutation causes neurodegeneration; it could simply be a very good marker for the disease," Olby says. "Our next step will be to determine exactly how the mutation affects the protein Rab 24 and its function and to determine whether this results in neuron death. This gene will also be investigated in humans with hereditary ataxia."