Muscular dystrophy (MD) refers to a diverse group of inherited muscle disorders characterized by skeletal muscle degeneration, regeneration, and ultimately loss of muscle function. More than 30 different genes have been identified in humans, that when mutated, are responsible for different forms of muscular dystrophies. Many of those genes encode proteins which are important for maintaining integrity of sarcolemmal membrane structures (Figure 1). The most common forms of MDs in humans are Duchenne Muscular Dystrophy (DMD), which is caused by deficiency in intracellular protein dystrophin; Laminin α 2 deficient Muscular Dystrophy (LDMD), caused by a deficiency in the extracellular protein laminin α 2; and muscular dystrophies caused by deficiency in dystrophin associated glycoproteins (DAGP). DAGP is composed of the membrane proteins - α β,γ,and δ sarcoglycan and α and β dystroglycan. Deficiency in DAGP is associated with several forms of Limb Girdle Muscular Dystrophy (LGMD).

Figure 1. Dystrophin and Associated Proteins

Various forms of MD occur not only in humans, but also in other species, such as dogs and cats. A presumptive diagnosis of muscular dystrophy can be made from routine H&E staining of muscle biopsy specimens. The next question to be asked is “What type of muscular dystrophy is this”? as the long term prognosis can differ between different forms of muscular dystrophy.  The Comparative Neuromuscular Laboratory now offers testing for the immunodiagnosis of specific forms of MD in dogs and cats. We are currently using a panel of nine antibodies against muscular dystrophy proteins in immunofluorescence staining (figure 2) with confirmation by immunoblotting (figure 3).  Specific antibodies include those against dystrophin-rod domain and C-terminus, laminin α 2, utrophin, and spectrin, and antibodies against the sarcoglycans (α,β,γ,) and dystroglycan (β).  Using this panel of antibodies, we will be able to diagnose the most common forms of MD in dogs and cats.

Figure 3. Immunoblotting for muscular dystrophy proteins