Degenerative Myelopathy in Hovawart Dogs: Molecular Characterization, Pathological Features and Accumulation of Mutant Superoxide Dismutase 1 Protein

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

Studies on Disease spectrum and the localization of misfolded mutant SOD1 protein in the spinal cords of SOD1-related canine degenerative myelopathy

博士(獣医学)岐阜大学(Gifu University

Magnetic Resonance Imaging Diagnosis of Dandy-Walker-Like Syndrome in a Wire-Haired Miniature Dachshund

A 12-week-old female Wire-haired miniature dachshund presented with non-progressive ataxia and hypermetria. Due to the animal’s clinical history and symptoms, cerebellar malformations were suspected. Computed tomography (CT) and magnetic resonance imaging (MRI) detected bilateral ventriculomegaly, dorsal displacement of the cerebellar tentorium, a defect in the cerebellar tentorium and a large fluid-filled cystic structure that occupied the regions where the cerebellar vermis and occipital lobes are normally located. The abovementioned cystic structure and the defect in the cerebellar tentorium were comparable to those seen in humans with Dandy-Walker syndrome. However, the presence of the cystic structure in the occipital lobe region was unique to the present case. During necropsy, the MRI findings were confirmed, but the etiology of the condition was not determined

Prognostic value of serum cystatin C concentration in dogs with myxomatous mitral valve disease

Abstract Background Impaired renal function is 1 of the poor prognostic factors in dogs with myxomatous mitral valve disease (MMVD). However, the value of cystatin C (Cys‐C), a marker of renal function, as a prognostic marker for MMVD in dogs has not yet been explored. Objective This study aims to investigate the prognostic value of Cys‐C in dogs with MMVD. Animals Fifty client‐owned small‐breed dogs with MMVD were included in this study. Methods This is a retrospective, cross‐sectional study. The prognostic value of serum Cys‐C concentration was assessed using univariable and multivariable Cox hazard regression analyses. Kaplan‐Meier survival curves for MMVD‐specific survival in dogs stratified into high and low Cys‐C groups were generated and analyzed using the log‐rank test. Results Serum Cys‐C concentrations were significantly associated with MMVD‐related death (P < .01) in both univariable (hazard ratio [HR], 5.086; 95% confidence interval [CI], 1.950‐13.270) and multivariable Cox hazard regression analysis (HR, 4.657; 95% CI, 1.767‐12.270). The high Cys‐C group (n = 14) had a significantly shorter MMVD‐specific survival time than the low Cys‐C group (n = 36; P < .01). In dogs with normal blood creatinine concentrations, the high Cys‐C group (n = 10) had a significantly shorter MMVD‐specific survival time than the low Cys‐C group (n = 36; P < .01). Conclusions and Clinical Importance High serum Cys‐C concentrations were associated with a worse prognosis of MMVD. Furthermore, serum Cys‐C could be a predictor of MMVD prognosis even in dogs with normal blood creatinine concentration