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Keywords:

  • gene therapy;
  • heart;
  • laminin;
  • muscle;
  • muscular dystrophy

Abstract

Several approaches to treat laminin α2 chain–deficient congenital muscular dystrophy (MDC1A) in mouse models have been undertaken. Most have shown promising results in young animals. However, older animals have only been characterized to some extent. Herein we analyze the lifespan of laminin α2 chain–deficient mice with transgenic overexpression of laminin α1 chain. Further outcome measures included internalized myonuclei, heart fibrosis, grip strength, and serum creatine kinase activity. We show that laminin α2-chain–deficient animals that overexpress laminin α1 chain survive to up to 1.5–2 years of age. Furthermore, they displayed improved skeletal and heart muscle morphology, near-normal muscle strength, and normalized creatine kinase levels. Such an improvement of the dystrophic phenotype that persists to old age has not been previously demonstrated in mice. Our findings hold promise with regard to the efficient treatment of MDC1A patients in the future. Muscle Nerve, 2010