Profiling of mRNA in humans with Duchenne muscular dystrophy (DMD) shows an increase in Ctss (cathepsin S) expression in injured skeletal muscle.
This transgenic strain places mouse Ctss cDNA under the control of a modified human ACTA1 (actin, alpha 1, skeletal muscle) promoter. Expression has been demonstrated in the quadriceps, tibialis anterior, gastrocnemius, and flexor digitorum brevis. Expression is uniform in multiple skeletal muscles that are predominantly fast-twitch, although lower levels of expression are observed in the soleus with its greater slow-fiber content. The heart shows no expression.
Hemizygous mice show greater muscle Ctss proteolytic activity that is associated with the induction of increased myofiber necrosis, muscle histopathology, and functional deficits that are reminiscent of muscular dystrophy. Histological analysis of skeletal muscle from hemizygous mice shows disease at 2 months of age which is characterized by accumulation of central nuclei in presumed regenerating myofibers, fatty tissue replacement and fibrosis, all features of muscular dystrophy. Similar tissue histopathology, with increased quantitative indexes of disease, are observed in skeletal muscle at 10 months of age. A decline in functional performance is correlated with the pathogenic changes, as assessed by treadmill running at both 2 and 4 months of age.
Hemizygous males may be infertile, thus hemizygous female x non-carrier male crosses are recommended to maintain a colony.
