title: Degenerative myelopathy associated with a missense mutation in the superoxide dismutase 1 (SOD1) gene progresses to peripheral neuropathy in Pembroke Welsh corgis and boxers.
abstract: Canine degenerative myelopathy (DM) is an adult-onset, fatal neurodegenerative disease with many similarities to an upper-motor-neuron-onset form of human amyotrophic lateral sclerosis (ALS), that results from mutations in the superoxide dismutase (SOD1) gene. DM occurs in many dog breeds, including the Pembroke Welsh Corgi and Boxer. The initial upper motor neuron degeneration produces spastic paraparesis and affected dogs develop general proprioceptive ataxia in the pelvic limbs. Dog owners usually elect euthanasia when their dog becomes paraplegic. When euthanasia is delayed, lower motor neuron signs including ascending tetraparesis, flaccid paralysis and widespread muscle atrophy emerge. For this study, muscle and peripheral nerve specimens were evaluated at varying disease stages from DM-affected Pembroke Welsh Corgis and Boxers that were homozygous for the SOD1 mutation and had spinal cord histopathology consistent with DM. Comparisons were made with age- and breed-matched control dogs. Here we provide evidence that Pembroke Welsh Corgis and Boxers with chronic DM develop muscle atrophy consistent with denervation, peripheral nerve pathology consistent with an axonopathy, and to a lesser degree demyelination. Canine DM has been proposed as a potential spontaneous animal disease model of human ALS. The results of this study provide further support that canine DM recapitulates one form of the corresponding human disorder and should serve as a valuable animal model to develop therapeutic strategies.
authors.affiliation: Department of Pathology, School of Medicine, University of California San Diego, La Jolla, CA 92093-0709, USA. gshelton@ucsd.edu
authors.forename: G Diane
authors.initials: GD
authors.lastname: Shelton
authors.forename: Gayle C
authors.initials: GC
authors.lastname: Johnson
authors.forename: Dennis P
authors.initials: DP
authors.lastname: O'Brien
authors.forename: Martin L
authors.initials: ML
authors.lastname: Katz
authors.forename: Jill P
authors.initials: JP
authors.lastname: Pesayco
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Chang
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Mizisin
authors.forename: Joan R
authors.initials: JR
authors.lastname: Coates
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D004283:Dog Diseases / Q000201:enzymology / Q000235:genetics*; D004285:Dogs; D020022:Genetic Predisposition to Disease / Q000235:genetics; D020271:Heredodegenerative Disorders, Nervous System / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D006720:Homozygote; D020125:Mutation, Missense / Q000235:genetics*; D010523:Peripheral Nervous System Diseases / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D013118:Spinal Cord Diseases / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D013482:Superoxide Dismutase / Q000172:deficiency / Q000235:genetics*; D000072105:Superoxide Dismutase-1
chemical_list: C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1