01212-A: Phenotypic Characterization of Peripheral Nerve Disease in Degenerative Myelopathy Dogs

Grant Status: Closed

Grant Amount: $12,092
Dr. Joan R. Coates, DVM, University of Missouri, Columbia
January 1, 2009 - June 30, 2010
Sponsor(s): American Bullmastiff Association, American German Shepherd Dog Charitable Foundation, Inc., Briard Club of America Health & Education Trust, Clumber Spaniel Club of America, Delaware County Kennel Club, English Setter Association of America, Inc., Flat-Coated Retriever Foundation, French Bulldog Rescue League, Golden Retriever Foundation, Greyhound Club of America, Health & Rescue Foundation of the Petit Basset Griffon Vendeen Club of America, Irish Terrier Club of America, Labrador Retriever Club, Leonberger Health Foundation, National Amateur Retriever Club, Poodle Club of America Foundation, Saluki Health Research, Inc., Scottish Terrier Club of America, Siberian Husky Club of America, United States Australian Shepherd Foundation
Breed(s): Rhodesian Ridgeback, Chesapeake Bay Retriever, German Shepherd Dog, Boxer, Cardigan Welsh Corgi
Research Program Area: Treatment

Project Summary

Degenerative myelopathy (DM) is a disease of the spinal cord causing progressive weakness in the hind limbs which progresses to affect the front limbs and shows signs also in the muscles and nerves. Though most commonly reported in German Shepherds, high disease prevalence also exists in other breeds, such as Cardigan and Pembroke Welsh Corgis (PWC), Rhodesian Ridgebacks, and Boxer dogs. Genome-wide association mapping and a candidate gene approach identified a mutation in the canine SOD1 gene. Homozygosity for the mutant allele was associated with DM in five dog breeds which segregate for DM (Boxers, Pembroke Welsh Corgis, Rhodesian Ridgebacks, Chesapeake Bay Retrievers and German Shepherd dogs). Canine DM caused by SOD1 mutations resembles some forms of human ALS - Lou Gehrig's disease. Better characterization of the clinical disease spectrum in the DM affected dog, especially the nerve and muscle pathology will assist in establishing collaborations with ALS researchers and in development of therapeutic drug trials similar to those of human ALS. We hypothesize for this proposal that the nerve and muscle deterioration of canine DM will compare to that of human ALS. We are testing our hypothesis by performing clinical studies of the nerve and muscle and studying the pathology in DM affected dogs. The investigators were successful in obtaining matching funding from the ALS Association for completion of the proposed work. We have had opportunities to perform electrodiagnostic testing on 4 dogs prior to necropsy and 3 dogs early in the disease process. However, we have established a motor unit number estimation technique in dogs that will have potential use to measure disease progression when testing therapies. This work was funded by a University of Missouri Clinician Scientist Award. We have prepared a kit to collect quality samples for nerve and muscle evaluations. In total, we have collected 74 muscle and nerve specimens from various breeds of DM affected dogs and 49 control dogs of older age. We have decided to focus on two breeds, the Pembroke Welsh Corgi and Boxer due to sample numbers because these are the breeds from which we have received the greatest number of samples. Morphometric analysis has been completed and data analyzed. There is clear evidence for peripheral nerve disease both qualitatively and quantitatively in both breeds. Findings and discussions will be included in detail in the paper under preparation.

Publication(s)

Coates, Jr and Wininger, Fa (2010) Canine Degenerative Myelopathy. Veterinary Clinics of North America: Small Animal Practice. 40, 929-50. 10.1016/j.cvsm.2010.05.001 http://www.sciencedirect.com/science/article/B758P-50V16W9-H/2/0c642250433c68174360fbab19f7c03b Awano, T, Johnson, Gs, Wade, Cm, Katz, Ml, Johnson, Gc, Taylor, Jf, Perloski, M, Biagi, T, Baranowska, I, Long, S, March, Pa, Olby, Nj, Shelton, Gd, Khan, S, O'brien, Dp, Lindblad-Toh, K and Coates, Jr (2009) Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis. Proceedings of the National Academy of Sciences. 106, 2794-9. 10.1073/pnas.0812297106 http://www.pnas.org/content/106/8/2794.abstract March, Pa, Coates, Jr, Abyad, Rj, Williams, Da, O'brien, Dp, Olby, Nj, Keating, Jh and Oglesbee, M (2009) Degenerative Myelopathy in 18 Pembroke Welsh Corgi Dogs. Veterinary Pathology Online. 46, 241-50. 10.1354/vp.46-2-241 http://vet.sagepub.com/content/46/2/241.abstract Coates, Jr, March, Pa, Oglesbee, M, Ruaux, Cg, Olby, Nj, Berghaus, Rd, O'brien, Dp, Keating, Jh, Johnson, Gs and Williams, Da (2007) Clinical Characterization of a Familial Degenerative Myelopathy in Pembroke Welsh Corgi Dogs. Journal of Veterinary Internal Medicine. 21, 1323-31. http://dx.doi.org/10.1111/j.1939-1676.2007.tb01955.x

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