Canine Degenerative Myelopathy – Pathogenesis, Current Diagnostics Possibilities and Breeding Implications Regarding Genetic Testing (original) (raw)
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DEGENERATIVE MYELOPATHY IN DOGS
One of the chronic progressive disorders of the spinal cord in dogs is the degenerative myelopathy (DM). The most predisposed age in dog is 5 to 14 years, while rarely noted in younger, there is no gender predisposition. This disorder most commonly appears in dogs of the German shepherd breed, but it can appear in other breeds too. The main changes about this disease are degeneration of the myelin, especially in the thoracic-lumbar segments of the spinal cord and the dorsal nerve roots. The progression of the disease is slow and can last months to years. Undoubtedly, diagnosis is made by examinations of the CSF and establishing elevated level of protein segments. Key words: dog, degenerative myelopathy, CSF
Revista Colombiana de Ciencias Pecuarias
Background: Canine degenerative myelopathy (DM) is a late-onset disease that primarily affects large-breed dogs. The disease involves the spinal cord and produces progressive paresia and, eventually, complete loss of mobility. DM has been related to missense mutation c.118G>A in the SOD1 gene. Objective: To determine the genotypic and genic frequencies of DM in Mexico. Methods: In total, 330 samples from 22 different dog breeds were genotyped using the polymerase chain reaction and restriction fragment length polymorphisms (PCR-RFLP) technique. Results: The mutation was identified in 71 animals from 11 different breeds. Observed genic frequencies were 0.78 for the G allele and 0.14 for the A allele. Genotypic frequencies were 0.79 for the G/G wild-type, 0.14 for the G/A heterozygote, and 0.7 for the A/A homozygote. Conclusion: The genic frequency of this allele is high among the studied populations. A molecular marker program that identifies the DM mutation in breeding dogs should be implemented in order to reduce this frequency.
Journal of Comparative Pathology
Degenerative myelopathy (DM) is an adult-onset, progressive neurological disease affecting several breeds of dog. Homozygosity or compound heterozygosity for the canine superoxide dismutase 1 (SOD1) gene mutations, possibly modulated by the modifier SP110 locus, are associated with a high risk for DM. Although the pathophysiological mechanisms are largely unknown, a role for mutant SOD1 in causing neuronal degeneration has been postulated. Three Hovawart dogs, 9e12 years of age, developed slowly progressive incoordination and weakness of the pelvic limbs leading to non-ambulatory flaccid paraparesis and muscle atrophy. Neuropathological lesions comprised axonal degeneration and loss of ascending and descending spinal pathways, which were most severe in the mid-to caudal thoracic segments. Accumulation of mutant SOD1 protein in neurons and reactive astrocytes was demonstrated by immunolabelling with the 16G9 antibody against the mutant SOD1 protein (p.E40K amino acid substitution). All three dogs were homozygous for the c.118A allele, but none had the SP110 'risk' haplotype, suggesting a weak association of SP110 with the onset of DM in this breed. Our data suggest that the Hovawart breed is predisposed to the SOD1:c.118G>A mutation, which is associated with the development of DM. Prevention of DM could be achieved with the help of strategies based on epidemiological and genetic testing.
Proceedings of The National Academy of Sciences, 2009
Canine degenerative myelopathy (DM) is a fatal neurodegenerative disease prevalent in several dog breeds. Typically, the initial progressive upper motor neuron spastic and general proprioceptive ataxia in the pelvic limbs occurs at 8 years of age or older. If euthanasia is delayed, the clinical signs will ascend, causing flaccid tetraparesis and other lower motor neuron signs. DNA samples from 38 DM-affected Pembroke Welsh corgi cases and 17 related clinically normal controls were used for genome-wide association mapping, which produced the strongest associations with markers on CFA31 in a region containing the canine SOD1 gene. SOD1 was considered a regional candidate gene because mutations in human SOD1 can cause amyotrophic lateral sclerosis (ALS), an adult-onset fatal paralytic neurodegenerative disease with both upper and lower motor neuron involvement. The resequencing of SOD1 in normal and affected dogs revealed a G to A transition, resulting in an E40K missense mutation. Homozygosity for the A allele was associated with DM in 5 dog breeds: Pembroke Welsh corgi, Boxer, Rhodesian ridgeback, German Shepherd dog, and Chesapeake Bay retriever. Microscopic examination of spinal cords from affected dogs revealed myelin and axon loss affecting the lateral white matter and neuronal cytoplasmic inclusions that bind anti-superoxide dismutase 1 antibodies. These inclusions are similar to those seen in spinal cord sections from ALS patients with SOD1 mutations. Our findings identify canine DM to be the first recognized spontaneously occurring animal model for ALS.
Veterinary World, 2021
Background and Aim: Canine degenerative myelopathy (CDM) is an adult-onset fatal disorder associated with a point mutation of the superoxide dismutase 1 (SOD1) gene (SOD1:c.118G>A). This study aimed to determine the allele and genotype frequencies of this mutation in a group of Belgian Malinois dogs in Greece. Materials and Methods: Samples (n=72) of whole blood were collected from 72 purebred dogs of the Hellenic Armed Forces; these samples were processed for DNA isolation, polymerase chain reaction, and digestion with the restriction endonuclease AcuI. Sample testing was conducted in compliance with ISO17025 accreditation requirements. Results: The observed relative genotype frequencies were 71% for the homozygous (GG), 25% for the heterozygous (AG), and 4% for the homozygous mutant (AA) alleles. These frequencies were close to those expected, indicating no significant departure from Hardy–Weinberg equilibrium (HWE, p=0.395). The frequency of heterozygous animals indicates that a high risk of developing CDM in forthcoming generations exists in the tested population because mating among carriers would result in 25% AA progeny. The medical record of the group of study animals indicated selection against leishmaniosis, as applied throughout generations by owners and breeders. The potential association of this selection with the HWE status of the study population was discussed. Conclusion: The SOD1:c.118G>A mutation was common in the tested group of dogs; thus, they are suitable for a follow-up investigation on the development and progression of CDM. A case-control study on animals with evidence of sensitivity to infectious myelopathy could provide new insights into disease pathogenesis.
Veterinary World, 2024
Background and Aim: Canine degenerative myelopathy (DM) is an autosomal recessive inherited disease that affects different dog breeds. It has an invariably fatal outcome once the clinical symptoms begin. This study aimed to investigate the population behavior of the mutation superoxide dismutase 1 (SOD1) c.118: G˃A responsible for the high risk of developing DM in two populations of German Shepherd dogs from Uruguay and Paraguay. Materials and Methods: A total of 158 German Shepherd dogs from Uruguay (n = 114) and Paraguay (n = 44) were analyzed. Genomic DNA was extracted from peripheral whole blood. The SOD1 c.118: G˃A mutation was identified by polymerase chain reaction-restriction fragment length polymorphism and subsequently validated using sequencing. Allelic and genotypic frequencies and Hardy–Weinberg equilibrium were calculated for both populations. The rate of clinical progression was evaluated in animals homozygous for the mutation. Results: The frequencies of allele A associated with a higher risk of DM, were 0.15 and 0.23 in Paraguay and Uruguay, respectively. Paraguay’s population was found to be in Hardy–Weinberg equilibrium (p = 1.00), whereas the population of dogs from Uruguay deviated from equilibrium (p = 0.008). When comparing the populations, no significant difference was observed in the distribution of genotypes (p = 0.26). When evaluating the clinical progression rate, all animals aged >10 years showed clinical symptoms compatible with DM. Conclusion: This study demonstrated for the first time the presence of the SOD1:c118 G>A mutation in German Shepherd dogs from Uruguay and Paraguay. The frequency detected in Uruguay was significant. Although the frequency was lower in Paraguay, the allele was present. This demonstrates the need to implement genotyping tests as part of a possible DM control program in both countries studied. Keywords: degenerative myelopathy, genetic disease, German Shepherd dog, superoxide dismutase 1 gene.