Canine degenerative myelopathy (DM) is a progressive and inevitably fatal neurological disease affecting members of different dog breeds and mixes. It is an inherited disease with an age-related penetrance. The risk of developing the disease when dogs are homozygous for the causal SOD1 variant allele is currently unknown but of great concern to dog breeders and owners. The proposed research will further define the risk for developing DM in genetically at-risk dogs with a health survey distributed to dog owners whose dogs have been tested for the risk factor allele. This work will also examine the molecular mechanisms responsible for disease onset and spread by comparing single-nucleus RNA expression patterns in specific cell types in dorsal root ganglia from normal dogs and from affected dogs at various stages of the disease.