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Transgenic overexpression of laminin α1 chain in laminin α2 chain–deficient mice rescues the disease throughout the lifespan
Author(s) -
Gawlik Kinga I.,
Durbeej Madeleine
Publication year - 2010
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.21616
Subject(s) - laminin , congenital muscular dystrophy , genetically modified mouse , transgene , creatine kinase , skeletal muscle , biology , endocrinology , muscular dystrophy , medicine , phenotype , microbiology and biotechnology , gene , genetics , extracellular matrix
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