Changes of skeletal muscle in young dystrophin-deficient cats: a morphological and morphometric study

Dystrophin deficiency causes Duchenne muscular dystrophy (DMD). Hypertrophi c feline muscular dystrophy (HFMD) is a homologous animal model of DMD. Our objective was to investigate the early changes caused by dystrophin defici ency in skeletal muscle of cats of 3-4 and 6-9 months. Obvious histological lesions were already present in the younger cats, and they increased in ma gnitude over time. They consisted of multifocal areas of degeneration and r egeneration with mononuclear infiltration, and a wide variation in myofiber diameter, as evidenced by significantly increased variability coefficients in muscle fiber size, myofiber splitting, central nuclei, and hypercontrac ted myofibers. Widespread multifocal mineralizations were frequently observ ed. Endomysial and perimysial fibrosis was not a feature observed in axial or appendicular muscles, but was present in the diaphragm of two cats at ne cropsy. There was a significant decrease in the number of type 2A myofibers in dystrophin-deficient cats at both ages. Sarcolemmal dystrophin was most ly absent in all dystrophin-deficient cats; however, a small percentage of fibers stained positive, accounting for a faint residual band in the immuno blot. Carrier females had a mosaic staining pattern with irregular staining in most fibers, or even absent staining in rare fibers. However, no histol ogical lesions were seen. Taken together, these data provide significant ba seline information for further studies on the early changes associated with dystrophin deficiency in cats, or use of young dystrophin-deficient cats i n therapeutic trials.