Genetic basis of Degenerative Myelopathy (DM) in Pembroke Welsh Corgis - is caused primarily by a mutation in the SOD1 gene. Dogs homozygous for the SOD1 mutation (inherit a mutated allele from both parents) are susceptible to developing DM, but not all do—indicating the action of modifier genes. The SP110 gene has been identified as a dominant modifier specifically in Pembroke Welsh Corgis. Dogs who are homozygous for the SOD1 mutation and carry at least one copy of the SP110 variant are at increased risk for early-onset DM. The SP110 variant is on chromosome 25 and is involved in gene transcription regulation. Without two copies of the SOD1 mutation, the SP110 variant has no effect on DM risk in the breed; thus, only those with the SOD1 risk should worry about SP110.
Pathophysiology - DM is a progressive neurodegenerative disorder akin to amyotrophic lateral sclerosis (ALS) in humans. It involves degeneration of white matter in the spinal cord, resulting in loss of coordination and progressive atrophy of hind limb muscles. Over time, the disease progresses to paralysis and loss of bladder and bowel control. The SP110 modifier accelerates the onset of these symptoms in genetically at-risk (SOD1 homozygous) Corgis.
Complications - Affected dogs ultimately experience severe mobility issues, progressing from hind limb weakness to paraplegia. Incontinence and involvement of the forelimbs occur as the disease advances. Most cases are not painful, but euthanasia is often considered when quality of life declines due to loss of mobility or continence. The condition can be mistaken for orthopedic issues like hip dysplasia, so genetic testing provides a definitive risk profile.
Why This Matters to Breeders and Vets - Breeders need to understand DM genetics to make informed mating choices and avoid producing high-risk puppies. Veterinarians must be aware of this risk to provide accurate prognoses, guidance on genetic counseling, and early intervention strategies for at-risk dogs. Early identification allows for improved planning, management, client education, and potentially longer, better quality of life for affected dogs.