myopathy in corgi dogs

myopathy in corgi dogs

corgi dogs
corgi dogs (Pembroke Welsh)

Signalment and History:
- 5-year-old, intact male, Pembroke Welsh Corgi research colony at Auburn’s Scott-Ritchey Research Center 24-hour history of progressive seizures Similar seizure activity noted in a specific family of corgi dogs History of mild ptyalism, dysphagia, muscle weakness - Euthanized

Necropsy Findings:
- BCS 3/9
- Marked muscle wasting
- Most significant, temporal muscles
- Marked hypertrophy of outermost 2-cm of the diaphragm (up to 2-cm)
- Pale streaking in skeletal muscles
- Heart grossly normal

Morphological Diagnosis:
Skeletal muscle, biceps femoris:
Moderate, chronic, diffuse, myocyte atrophy, necrosis, regeneration, fibrosis and mineralization

Etiological Diagnosis:
Hereditary muscular dystrophy
Duchenne-like Muscular Dystrophy
- An x-linked recessive inherited disease affecting dogs and people
- Individuals are unable to produce adequate amounts of dystrophin.

- Dystrophin:
- Cytoskeletal protein, localized in the sarcolemma
- Forms dystrophin-glycoprotein complex (DGC)
- Dystroglycan, sarcoglycan, and syntrophin/dystrobrevin complexes
- Acts as membrane stabilizer during muscle contraction.
- Complex associations link cytoskeletal protein actin to the basal lamina of muscle fibers

Pathophysiology:
- Loss of dystrophin - membrane becomes leaky
as a result of mechanical or hypoosmotic stress
- Ca2+ permeability increased, various Ca2+
depended proteases (i.e. calpain) activated
- Defect in DGC - muscle fiber necrosis -
inflammation - regeneration - progressive
replacement with fibrosis/fatty tissue

Murine models:
- Mdx mice
- Mdx52 mice
- Feline model:
- Hypertrophy feline muscular dystrophy (HFMD)


- Canine models:
- Golden Retriever muscular dystrophy (GRMD)
- Canine X-linked muscular dystrophy (CXMD)
- Cavalier King Charles spaniels with muscular
dystrophy (CKCS-MD)


- Pembroke Welsh corgi model
- Mutation - long interspersed repetitive element-1 (LINE-1) insertion in intron 13
- Introduces a new exon containing an in-frame stop codon.
- Clinical signs
- Generalized muscle atrophy, stiff shuffling gait, difficulty standing, exercise intolerance, hyperflexion of hock joint, dysphagia, ptyalism
- Dogs significantly smaller than littermates by 6 weeks.
- Clinical heart disease
- Classic histological lesions:
- Skeletal muscle - variable fiber size, central nucleation, mineralization, fibrosis, neutrophil, and macrophage infiltration.
- Cardiac muscle - focal vacuolar degeneration
- Carrier dogs display mild myopathy

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Reference

- Smith BF, Yue Y, Woods PR, Kornegay JN, Shin JH, Williams RR, Duan D. An intronic

LINE-1 element insertion in the dystrophin gene aborts dystrophin expression and results in Duchenne-like muscular dystrophy in the corgi dogs. Laboratory Investigation.

2011 Feb; 91(2):216-31.

- Akinori Nakamura and Shin'ichi Takeda. Mammalian Models of Duchenne Muscular

Dystrophy: Pathological Characteristics and Therapeutic Applications. Journal of Biomedicine and Biotechnology, vol. 2011. Article ID 184393, 8 pages, 2011.

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