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, 9–12 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.

退行性脊髓病 (DM) 是一种成年发病的进行性神经系统疾病，影响多种犬种。犬超氧化物歧化酶 1 ( SOD1 ) 基因突变的纯合子或复合杂合子，可能由修饰符SP110调节位点，与 DM 的高风险相关。虽然病理生理机制在很大程度上是未知的，但已经假设突变 SOD1 在引起神经元变性中的作用。三只 9-12 岁的 Hovawart 犬出现缓慢进行性的骨盆四肢不协调和虚弱，导致不能走动的弛缓性下肢轻瘫和肌肉萎缩。神经病理学损伤包括轴索变性和上行和下行脊柱通路的丧失，这在中至尾胸段最为严重。通过用 16G9 抗体对突变 SOD1 蛋白（p.E40K 氨基酸取代）进行免疫标记，证明了突变 SOD1 蛋白在神经元和反应性星形胶质细胞中的积累。所有三只狗都是c.118A等位基因纯合子，但没有一只狗具有SP110 “风险”单倍型，表明SP110与该品种的 DM 发病之间存在弱关联。我们的数据表明 Hovawart 品种易患SOD1:c.118G>A突变，这与 DM 的发展有关。可以借助基于流行病学和基因检测的策略来预防 DM。