Evaluation of the dystrophin-glycoprotein complex, alpha-actinin, dysferlin and calpain 3 in an autosomal recessive muscular dystrophy in Labrador retrievers.
Labrador retrievers suffer from an autosomal recessive muscular dystrophy of unknown aetiology. Dogs affected with this disease develop generalized weakness associated with severe, generalized skeletal muscle atrophy and mild elevations in creatine kinase in the first few months of life. The severity of signs tends to progress over the first year of life but can vary from mild exercise intolerance to non-ambulatory tetraparesis. Beyond 1 year of age, the signs usually stabilize and although muscle mass does not increase, affected dogs' strength may improve slightly. The pathological changes present on muscle biopsy include marked variation in muscle fibre size with hypertrophied and round atrophied fibres present. There is an increased number of fibres with central nuclei and split fibres can be seen. It has been suggested that the disorder is a model for limb-girdle muscular dystrophy. In recent years, mutations in genes encoding the proteolytic enzyme, calpain 3, a novel protein named dysferlin, and components of the dystrophin-glycoprotein complex have been identified as causes of autosomal recessive limb-girdle muscular dystrophy. We have evaluated these proteins in normal dogs and in three Labrador retrievers with autosomal recessive muscular dystrophy using immunohistochemistry and Western blot analysis on frozen skeletal muscle. The results demonstrate that dystrophin, the sarcoglycans, alpha-actinin, dysferlin and calpain 3 are present in the normal and affected dogs. We conclude that this autosomal recessive muscular dystrophy is not due to a deficiency of alpha-actinin, or any of the known autosomal recessive limb-girdle muscular dystrophy proteins, although we cannot rule out a malfunction of any of these proteins.
Olby
N J
NJ
Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
Sharp
N J
NJ
Anderson
L V
LV
Kunkel
L M
LM
Bönnemann
C G
CG
D000185:Actinin / Q000378:metabolism*; D000818:Animals; D002154:Calpain / Q000378:metabolism*; D004283:Dog Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004285:Dogs; D000073939:Dysferlin; D016189:Dystrophin / Q000378:metabolism*; D005260:Female; D005808:Genes, Recessive / Q000235:genetics; D006023:Glycoproteins / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009137:Muscular Dystrophy, Animal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
C114839:DYSF protein, human; D000073939:Dysferlin; D016189:Dystrophin; D006023:Glycoproteins; D008565:Membrane Proteins; D009124:Muscle Proteins; D000185:Actinin; D002154:Calpain