Abstract
BackgroundDegenerative myelopathy (DM) is a progressive neurodegenerative disease frequently found in Pembroke Welsh Corgis (PWCs). Most DM-affected PWCs are homozygous for the mutant superoxide dismutase 1 (SOD1) allele; however, the genetic examination for the SOD1 mutation does not exclusively detect symptomatic dogs. In order to identify novel biomarkers, the plasma microRNA (miRNA) profiles of PWCs with DM were investigated.ResultsQuantification of the plasma levels of 277 miRNAs by an RT-qPCR array identified 11 up-regulated miRNAs and 7 down-regulated miRNAs in DM-affected PWCs from those in wild-type SOD1 PWCs. A pathway analysis identified 3 miRNAs: miR-26b, miR-181a, and miR-196a, which potentially regulate several genes associated with SOD1. In order to validate the diagnostic accuracy of the candidate miRNAs in the aged PWC population, candidate miRNAs in plasma were measured by RT-qPCR and a receiver operating characteristic (ROC) curve analysis was performed. miR-26b had the largest area under the ROC curve for distinguishing DM PWCs from healthy PWCs (sensitivity, 66.7%; specificity, 87.0%). The plasma level of miR-26b was significantly higher in the DM group than in the healthy control group. A positive correlation was observed between increases in the plasma level of miR-26b and disease progression.ConclusionsThese results suggest that plasma miR-26b is a potential novel diagnostic biomarker of DM.
Highlights
Degenerative myelopathy (DM) is a progressive neurodegenerative disease frequently found in Pembroke Welsh Corgis (PWCs)
Canine degenerative myelopathy (DM) is an adult-onset progressive neurodegenerative spinal cord disorder that occurs in multiple dog breeds including Boxers, German Shepherds, and Pembroke Welsh Corgis (PWCs) [1, 2]
PWCs were diagnosed with DM at the Animal Medical Center of Gifu University according to the following criteria: clinical signs consistent with DM [2, 10], unremarkable findings on spinal imaging with magnetic resonance imaging (MRI) (0.4-Tesla APERTO Eterna, Hitachi), cerebrospinal fluid (CSF) analyses, and genetic testing proving homozygosity for the superoxide dismutase 1 (SOD1) c.118G > A missense mutation (A/A) [12]
Summary
Degenerative myelopathy (DM) is a progressive neurodegenerative disease frequently found in Pembroke Welsh Corgis (PWCs). Canine degenerative myelopathy (DM) is an adult-onset progressive neurodegenerative spinal cord disorder that occurs in multiple dog breeds including Boxers, German Shepherds, and Pembroke Welsh Corgis (PWCs) [1, 2]. A pre-mortem diagnosis is currently based on three steps: pattern recognition of the progression of clinical signs, genetic testing for the SOD1 mutation, and eliminating other diseases affecting the spinal cord [2, 10]. Homozygosity for the E40K SOD1 mutation has been identified as a major risk factor for DM, many dogs homozygous for the mutation do not develop clinical signs [12, 13]. The development of diagnostic biomarkers of DM is important in order to more accurately differentiate DM from other neurological diseases with a similar clinical presentation
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