OMIA 000679-9615 : Muscular dystrophy in Canis lupus familiaris

In other species: chicken , sheep , turkey , American mink , domestic cat

Possibly relevant human trait(s) and/or gene(s) (MIM number): 310200

Mendelian trait/disorder: unknown

Considered a defect: yes

Cross-species summary: Degenerative muscle disorder, leading to muscle weakness, liberation of myoglobin into the circulation from skeletal muscle, and subsequent wasting and possible contracture.

Species-specific description: This is the canine homologue of human Duchenne muscular dystrophy, which is caused by mutations in the dystrophin gene and is characterized by progressive weakness and muscle wasting that is ultimately fatal. Clinical signs begin at 8-10 weeks of age. Absence of the dystrophin protein causes sarcolemma dysfunction, muscular hypercontraction, and ultimately, muscle fiber degeneration. The mode of inheritance is X-linked recessive. Genetic tests are available.

Edited by Meg Sleeper, VMD and Vicki N. Meyers-Wallen, VMD, PhD, Dipl. ACT

History: The first identified case of canine muscular dystrophy was in a Golden Retriever in 1958 (Shelton et al., 2004).

Inheritance: Carrier females usually do not show clinical signs. However, due to random X inactivation, they can occasionally present with limb weakness and highly elevated serum creatine kinase, or show changes on electromyography or biopsy (Shelton et al., 2004; Kornegay et al., 2011).

Mapping: CFX

Molecular basis: All causative mutations occur within the dystrophin gene, although the molecular basis of the dystrophin mutation may be different between breeds. In the Golden Retriever, there is a point mutation in the consensus splice acceptor site in exon 6 of the dystrophin gene, such that exon 7 is skipped during mRNA processing. The amino acid frame shift causes premature termination of the dystrophin protein (Sharp et al., 1992; Bartlett at al., 1996; Howell et al., 1997).

Clinical features: Affected dogs develop clinical signs at 8 to 10 weeks of age. Signs include a shuffling gait or shortened stride (“bunny hopping”), inability to completely open the jaw, difficulty eating, thickening of the base of the tongue, excessive salivation, abduction of front paws, adduction of stifles and hocks, and prominent wasting of temporal and trunk muscles (Shelton, 2004; Valentine et al., 1992; Kornegay et al., 2011). Other signs include spinal and costal curvature, resulting in a crouched posture (Valentine et al., 1992). Elevated serum creatine kinase concentrations (up to 300 times greater than normal) begins during the first week of life age, and is exacerbated by exercise (Valentine et al., 1992). In breeds where a mutation has not been reported, affected dogs can be tentatively diagnosed by immunohistochemical tests for the presence or absence of dystrophin protein in skeletal muscle biopsy (Shelton and Engvall 2002).

Pathology: Clinical signs are caused by the absence of dystrophin protein. Affected animals initially have sarcolemma dysfunction, which results in an increased intracellular calcium and muscle fiber hypercontraction. These are followed by muscle fiber degeneration and necrosis, with some regeneration (Howell et al., 1997). Eventually, muscle fibrosis, mineralization and fat infiltration occur in both skeletal and cardiac muscle. Lesions in cardiac muscle, which are analogous but can be less severe, are usually in the ventricles, and usually occur after 6 months of age (Howell et al., 1997).

Prevalence: Muscular dystrophy in the Golden Retriever (GRMD) has received most study (Kornegay et al., 2011), but has been identified in several breeds.

Control: Female relatives of affected dogs should be tested to identify carriers. Breeding of affected or carrier animals should be avoided.

Genetic testing: Causative mutations are known in the Golden Retriever, Rottweiler, German Shorthaired Pointer, and Cavalier King Charles Spaniel. A PCR-based test is available to detect the mutation in these breeds.

Breeds: Brittany Spaniel, Cavalier King Charles Spaniel, German Shorthair Pointer, Golden Retriever, Grand Basset Griffon Vendeen, Irish Terrier, Labrador Retriever, Miniature Schnauzer, Pembroke Welsh Corgi, Rat Terrier, Rottweiler, Samoyed, Weimaraner.

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2011 Kornegay, JN., Bogan, JR., Bogan, DJ., Childers, MK., Grange, RW. :
Golden retriever muscular dystrophy (GRMD): Developing and maintaining a colony and physiological functional measurements. Methods Mol Biol 709:105-23, 2011. Pubmed reference: 21194024. DOI: 10.1007/978-1-61737-982-6_7.
2005 Shelton, GD., Engvall, E. :
Canine and feline models of human inherited muscle diseases. Neuromuscul Disord 15:127-38, 2005. Pubmed reference: 15694134. DOI: 10.1016/j.nmd.2004.10.019.
2002 Shelton, G.D., Engvall, E. :
Muscular dystrophies and other inherited myopathies Veterinary Clinics of North America - Small Animal Practice 32:103-+, 2002.
2000 Klopp, L.S., Smith, B.F. :
Autosomal recessive muscular dystrophy in Labrador retrievers Compendium on Continuing Education for the Practicing Veterinarian 22:121-+, 2000.
1998 Hanson, S.M., Smith, M.O., Walker, T.L., Shelton, G.D. :
Juvenile-onset distal myopathy in rottweiler dogs Journal of Veterinary Internal Medicine 12:103-108, 1998. Pubmed reference: 9560767.
1997 Howell, J.M., Fletcher, S., Kakulas, B.A., Ohara, M., Lochmuller, H., Karpati, G. :
Use of the dog model for duchenne muscular dystrophy in gene therapy trials Neuromuscular Disorders 7:325-328, 1997. Pubmed reference: 9267846.
1996 Bartlett, R.J., Winand, N.J., Secore, S.L., Singer, J.T., Fletcher, S., Wilton, S., Bogan, D.J., Metcalfbogan, J.R., Bartlett, W.T., Howell, J.M., Cooper, B.J., Kornegay, J.N. :
Mutation segregation and rapid carrier detection of X-linked muscular dystrophy in dogs American Journal of Veterinary Research 57:650-654, 1996. Pubmed reference: 8723876.
1994 Gorospe, J.R.M., Tharp, M.D., Hinckley, J., Kornegay, J.N., Hoffman, E.P. :
A Role for Mast Cells in the Progression of Duchenne Muscular Dystrophy - Correlations in Dystrophin-Deficient Humans, Dogs, and Mice Journal of the Neurological Sciences 122:44-56, 1994. Pubmed reference: 8195802.
Kornegay, J.N., Sharp, N.J.H., Schueler, R.O., Betts, C.W. :
Tarsal joint contracture in dogs with golden retriever muscular dystrophy Laboratory Animal Science 44:331-333, 1994. Pubmed reference: 7983843.
Pacioretty, L.M., Cooper, B.J., Gilmour, R.F. :
Reduction of the transient outward potassium current in canine X-linked muscular dystrophy Circulation 90:1350-1356, 1994. Pubmed reference: 8087945.
Prattis, S.M., Horton, S.B., Vancamp, S.D., Kornegay, J.N. :
Immunohistochemical Detection of Neural Cell Adhesion Molecule and Laminin in X-Linked Dystrophic Dogs and Mdx Mice Journal of Comparative Pathology 110:253-266, 1994. Pubmed reference: 8040390.
Wilson, L.A., Cooper, B.J., Dux, L., Dubowitz, V., Sewry, C.A. :
Expression of utrophin (dystrophin-related protein) during regeneration and maturation of skeletal muscle in canine X- linked muscular dystrophy Neuropathology and Applied Neurobiology 20:359-367, 1994. Pubmed reference: 7808586.
Wilson, L.A., Dux, L., Cooper, B.J., Dubowitz, V., Sewry, C.A. :
Experimental Regeneration in Canine Muscular Dystrophy .2. Expression of Myosin Heavy Chain Isoforms Neuromuscular Disorders 4:25-37, 1994. Pubmed reference: 7513568.
1993 Anderson, J.E., Kakulas, B.A., Jacobsen, P.F., Johnsen, R.D., Kornegay, J.N., Grounds, M.D. :
Comparison of Basic Fibroblast Growth Factor in X-Linked Dystrophin-Deficient Myopathies of Human, Dog and Mouse Growth Factors 9:107-121, 1993. Pubmed reference: 8217214.
Prattis, S.M., Gebhart, D.H., Dickson, G., Watt, D.J., Kornegay, J.N. :
Magnetic Affinity Cell Sorting (MACS) Separation and Flow Cytometric Characterization of Neural Cell Adhesion Molecule- Positive, Cultured Myogenic Cells from Normal and Dystrophic Dogs Experimental Cell Research 208:453-464, 1993. Pubmed reference: 8375474. DOI: 10.1006/excr.1993.1267.
1992 Sharp, N.J.H., Kornegay, J.N., Vancamp, S.D., Herbstreith, M.H., Secore, S.L., Kettle, S., Hung, W.Y., Constantinou, C.D., Dykstra, M.J., Roses, A.D., Bartlett, R.J. :
An Error in Dystrophin Messenger RNA Processing in Golden Retriever Muscular Dystrophy, an Animal Homologue of Duchenne Muscular Dystrophy Genomics 13:115-121, 1992. Pubmed reference: 1577476.
Valentine, B.A., Winand, N.J., Pradhan, D., Moise, N.S., Delahunta, A., Kornegay, J.N., Cooper, B.J. :
Canine X-Linked Muscular Dystrophy as an Animal Model of Duchenne Muscular Dystrophy - A Review American Journal of Medical Genetics 42:352-356, 1992. Pubmed reference: 1536178. DOI: 10.1002/ajmg.1320420320.
1991 Mccully, K., Giger, U., Argov, Z., Valentine, B., Cooper, B., Chance, B., Bank, W. :
Canine X-Linked Muscular Dystrophy Studied with Invivo Phosphorus Magnetic Resonance Spectroscopy Muscle & Nerve 14:1091-1098, 1991. Pubmed reference: 1745283. DOI: 10.1002/mus.880141109.
Mehta, J.R., Braund, K.G., Hegreberg, G.A., Thukrall, V. :
Lipid Fluidity and Composition of the Erythrocyte Membrane from Healthy Dogs and Labrador Retrievers with Hereditary Muscular Dystrophy Neurochemical Research 16:129-135, 1991. Pubmed reference: 1908955.
Valentine, B.A., Chandler, S.K., Cummings, J.F., Cooper, B.J. :
Invitro Characteristics of Normal and Dystrophic Skeletal Muscle from Dogs American Journal of Veterinary Research 52:104-107, 1991. Pubmed reference: 2021236.
1990 Cooper, B.J., Gallagher, E.A., Smith, C.A., Valentine, B.A., Winand, N.J. :
Mosaic Expression of Dystrophin in Carriers of Canine X-Linked Muscular Dystrophy Laboratory Investigation 62:171-178, 1990. Pubmed reference: 2406503.
1989 Valentine, B.A., Cummings, J.F., Cooper, B.J. :
Development of Duchenne-Type Cardiomyopathy - Morphologic Studies in a Canine Model American Journal of Pathology 135:671-678, 1989. Pubmed reference: 2679113.
Valentine, B.A., Kornegay, J.N., Cooper, B.J. :
Clinical Electromyographic Studies of Canine X-Linked Muscular Dystrophy American Journal of Veterinary Research 50:2145-2147, 1989. Pubmed reference: 2610444.

Edit History


  • Created by Frank Nicholas on 06 Sep 2005
  • Changed by Martha MaloneyHuss on 06 Sep 2011
  • Changed by Vicki Meyers-Wallen on 18 Sep 2011
  • Changed by Frank Nicholas on 28 Sep 2011