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

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.

Molecular Surveillance of Canine Degenerative Myelopathy in Breeding Kennels from Romania

“…A study conducted in Brazil estimated the frequency of the mutant allele to be 0.12 in the German Shepherd breed [ 16 ]. In the United Kingdom, the mutant allele frequency in a reference population of German Shepherds was estimated to be 0.38 [ 26 ], while in Japan it was determined to be 0.22 [ 27 ]. In the USA, the mutant allele frequency was 0.36 [ 22 ] and 0.33 [ 28 ] in the German Shepherd population, while in Poland it was 0.18 and in Israel it was 0.17 [ 28 ].…”

Common Neurologic Diseases in Geriatric Dogs

“…Degenerative myelopathy (DM) is one of the most common chronic diseases of the spinal cord in dogs and has been known for more than 50 years [ 84 ]. The overall prevalence of the disease among all dogs is estimated at 0.19%, although due to its genetic origin, the prevalence varies widely among breeds and countries [ 85 , 86 , 87 , 88 ]. DM is an adult-onset (usually older than 8 years at the onset of clinical signs) chronic, progressive neurodegenerative disease with an autosomal recessive with incomplete penetrance mode of inheritance (OMIA 000263-9615), occurring primarily in large-breed dogs [ 87 ].…”

“…The overall prevalence of the disease among all dogs is estimated at 0.19%, although due to its genetic origin, the prevalence varies widely among breeds and countries [ 85 , 86 , 87 , 88 ]. DM is an adult-onset (usually older than 8 years at the onset of clinical signs) chronic, progressive neurodegenerative disease with an autosomal recessive with incomplete penetrance mode of inheritance (OMIA 000263-9615), occurring primarily in large-breed dogs [ 87 ]. It was initially described in German Shepherds but has now been reported in several pure- and mixed-breed dogs such as Pembroke Welsh Corgis, Boxers, Rhodesian Ridgebacks, Collies, and Bernese Mountain Dogs [ 84 , 89 , 90 ].…”