Molecular Epidemiological Survey for Degenerative Myelopathy in German Shepherd Dogs in Japan: Allele Frequency and Clinical Progression Rate

SIMPLE SUMMARY: Canine degenerative myelopathy (DM) is an adult-onset, chronic, progressive neurodegenerative disease caused by a DM-associated mutation (SOD1:c.118G>A, p.E40K) that commonly occurs in German Shepherd Dogs (GSDs). This study aimed to determine the mutant allele frequency in the Japanese GSD population and to analyze the clinical progression rate among GSDs with the homozygous mutant A/A genotype. The survey found 330 G/G dogs (61%), 184 G/A dogs (34%), and 27 A/A dogs (5%) among the 541 dogs examined, indicating that the mutant allele frequency was 0.220; the Japanese GSD population can be considered to be in Hardy–Weinberg equilibrium. Clinical analysis revealed that the clinical progression rate was particularly high (100%) among A/A dogs aged >10 years. Appropriate mating management is crucial for the management and prevention of DM in the Japanese GSD population. ABSTRACT: Canine degenerative myelopathy (DM) is an adult-onset, chronic, progressive neurodegenerative disease reported in multiple canine breeds, including the German Shepherd Dog (GSD). Clinical signs include progressive motor neuron paralysis, which begins in the pelvic limbs and eventually leads to respiratory distress, which may necessitate euthanasia. A common DM-associated mutation is a single nucleotide substitution that causes an amino acid substitution (c.118G>A, p.E40K) in the canine SOD1 gene. This SOD1 mutation and the clinical progression rate of A/A risk genotype in the Japanese GSD population have not been analyzed before. Therefore, the aim of this study was to determine the frequency of the mutated allele and analyze the clinical progression rate in the Japanese GSD population. We studied 541 GSDs registered with the Japanese German Shepherd Dog Registration Society between 2000 and 2019. Genotyping was performed using real-time PCR with DNA extracted from the hair roots of each dog. The study revealed 330 G/G dogs (61%), 184 G/A dogs (34%), and 27 A/A dogs (5%), indicating a frequency of the mutant allele of 0.220, which are in Hardy–Weinberg equilibrium. We analyzed the clinical signs in A/A dogs with an age limit of 10 years based on information obtained from the dogs’ owners. Of the seven A/A dogs older than 10 years, owners reported DM-related clinical signs, indicating a clinical progression rate of 100%. These results, further genotyping, and thorough clinical examinations of SOD1 A/A risk genotype will help control and prevent DM in the Japanese GSD population.