Immunohistochemical Observation of Canine Degenerative Myelopathy in Two Pembroke Welsh Corgi Dogs

Ogawa, Mizuki; Uchida, Katsuhisa; Park, Eun-Sil; Kamishina, Hiroaki; Sasaki, Jun; Chang, Hye-Sook; Yamato, Osamu; Nakayama, Hiroyuki

doi:10.1292/jvms.11-0097

Cited by 26 publications

(36 citation statements)

References 17 publications

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“…This confirms our earlier histopathologic demonstration of cytoplasmic SOD1 aggregate accumulation in the motor neurons from the spinal cords of DM-affected dogs 4,11. Ogawa et al16 have independently shown similarly appearing SOD1 aggregates in spinal cords from Pembroke Welsh Corgis with DM. As shown in Table3, cytoplasmic aggregates containing SOD1 antigen were found in spinal cord neurons in all but 1 of the examined dogs with histopathologically confirmed DM.…”

Section: Discussionsupporting

confidence: 90%

Breed Distribution of SOD1 Alleles Previously Associated with Canine Degenerative Myelopathy

Zeng

Coates

Johnson

et al. 2014

Veterinary Internal Medicne

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BackgroundPrevious reports associated 2 mutant SOD1 alleles (SOD1:c.118A and SOD1:c.52T) with degenerative myelopathy in 6 canine breeds. The distribution of these alleles in other breeds has not been reported.ObjectiveTo describe the distribution of SOD1:c.118A and SOD1:c.52T in 222 breeds.AnimalsDNA from 33,747 dogs was genotyped at SOD1:c.118, SOD1:c.52, or both. Spinal cord sections from 249 of these dogs were examined.MethodsRetrospective analysis of 35,359 previously determined genotypes at SOD1:c.118G>A or SOD1:c.52A>T and prospective survey to update the clinical status of a subset of dogs from which samples were obtained with a relatively low ascertainment bias.ResultsThe SOD1:c.118A allele was found in cross-bred dogs and in 124 different canine breeds whereas the SOD1:c.52T allele was only found in Bernese Mountain Dogs. Most of the dogs with histopathologically confirmed degenerative myelopathy were SOD1:c.118A homozygotes, but 8 dogs with histopathologically confirmed degenerative myelopathy were SOD1:c.118A/G heterozygotes and had no other sequence variants in their SOD1 amino acid coding regions. The updated clinical conditions of dogs from which samples were obtained with a relatively low ascertainment bias suggest that SOD1:c.118A homozygotes are at a much higher risk of developing degenerative myelopathy than are SOD1:c.118A/G heterozygotes.Conclusions and Clinical ImportanceWe conclude that the SOD1:c.118A allele is widespread and common among privately owned dogs whereas the SOD1:c.52T allele is rare and appears to be limited to Bernese Mountain Dogs. We also conclude that breeding to avoid the production of SOD1:c.118A homozygotes is a rational strategy.

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Section: Discussionsupporting

confidence: 90%

Breed Distribution of SOD1 Alleles Previously Associated with Canine Degenerative Myelopathy

Zeng

Coates

Johnson

et al. 2014

Veterinary Internal Medicne

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“…Our findings, in conjunction with those of Ogawa et al () and Zhou et al () indicate that, for the intercostal muscles, muscle atrophy and sensory neuron degeneration precede the degeneration of the associated MNs. Whether this is the case for other motor units in DM remains to be determined.…”

Section: Discussionsupporting

confidence: 90%

Characterization of thoracic motor and sensory neurons and spinal nerve roots in canine degenerative myelopathy, a potential disease model of amyotrophic lateral sclerosis

Morgan

Coates

Johnson

et al. 2013

J of Neuroscience Research

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Canine Degenerative Myelopathy (DM) is a progressive adult-onset multisystem degenerative disease with many features in common with amyotrophic lateral sclerosis (ALS). As with some forms of ALS, DM is associated with mutations in superoxide dismutase 1 (SOD1). Clinical signs include general proprioceptive ataxia and spastic upper motor neuron paresis in pelvic limbs, which progress to flaccid tetraplegia and dysphagia. The purpose of this study was to characterize DM as a potential disease model for ALS. We previously reported that intercostal muscle atrophy develops in dogs with advanced stage DM. To determine if other components of the thoracic motor unit (MU) also demonstrated morphological changes consistent with dysfunction, histopathologic and morphometric analyses were conducted on thoracic spinal motor neurons (MN) and dorsal root ganglia (DRG), and in motor and sensory nerve root axons from DM-affected Boxers and Pembroke Welsh Corgis (PWCs). No alterations in MNs, or motor root axons were observed in either breed. However, advanced stage PWCs exhibited significant losses of sensory root axons, and numerous DRG sensory neurons displayed evidence of degeneration. These results indicate that intercostal muscle atrophy in DM is not preceded by physical loss of the motor neurons innervating these muscles, or of their axons. Axonal loss in thoracic sensory roots and sensory nerve death suggest sensory involvement may play an important role in DM disease progression. Further analysis of the mechanisms responsible for these morphological findings would aid in the development of therapeutic intervention for DM and some forms of ALS.

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“…These functions of astrocytes are known to be impaired in ALS (Howland et al, 2002;Clement et al, 2003;Yamanaka et al, 2008). The expression of inducible nitric oxide synthase in SOD1-positive astrocytes was previously reported in DM (Ogawa et al, 2011). The loss of glutamate transporter 1 was more recently demonstrated in the astrocytes of DM cases (Ogawa et al, 2014).…”

Section: Discussionmentioning

confidence: 85%

“…It currently remains unknown whether the accumulation of insoluble proteins represents the final step in degenerated neurons or the progression of pathological changes. Awano et al reported the presence of SOD1 aggregates in the spinal neurons of dogs with DM (Awano et al, 2009); however, this finding was not confirmed in a later study (Ogawa et al, 2011). The discrepancy may stem from the specificity of the antibody used.…”

Section: Discussionmentioning

confidence: 86%

Accumulation and aggregate formation of mutant superoxide dismutase 1 in canine degenerative myelopathy

et al. 2015

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Immunohistochemical Observation of Canine Degenerative Myelopathy in Two Pembroke Welsh Corgi Dogs

Cited by 26 publications

References 17 publications

Breed Distribution of SOD1 Alleles Previously Associated with Canine Degenerative Myelopathy

Breed Distribution of SOD1 Alleles Previously Associated with Canine Degenerative Myelopathy

Characterization of thoracic motor and sensory neurons and spinal nerve roots in canine degenerative myelopathy, a potential disease model of amyotrophic lateral sclerosis

Accumulation and aggregate formation of mutant superoxide dismutase 1 in canine degenerative myelopathy

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