Mouse models of muscular dystrophy show a compensatory increase in the protein encoded by the Serpina3n (serine (or cysteine) peptidase inhibitor, clade A, member 3N) gene after acute muscle tissue injury.
These healthy transgenic mice express mouse Serpina3n under the regulatory control of the human ACTA1 (actin, alpha 1, skeletal muscle; also known as SKA) promoter. Expression has been demonstrated in fast skeletal muscles including the quadriceps, tibialis anterior, gastrocnemius, and flexor digitorum brevis. More slow/oxidative fiber-type muscles, such as the soleus and diaphragm, show lower levels of protein over-expression and the heart shows no transgene expression. Muscle histology appears normal at both 6 weeks and 10 months of age.
The transgene dramatically reduces skeletal muscle pathogenesis in both Sgcd (δ-sarcoglycan deficient; e.g. Stock No. 004582) and Dmdmdx (dystrophin deficient) mouse models of muscular dystrophy. Muscle degeneration and fibrosis are mitigated, creatine kinase serum levels are reduced, running capacity is restored, and in vivo muscle membrane leakiness is reduced.
