Research ArticleMuscular Dystrophy

Linker proteins restore basement membrane and correct LAMA2-related muscular dystrophy in mice

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Science Translational Medicine  28 Jun 2017:
Vol. 9, Issue 396, eaal4649
DOI: 10.1126/scitranslmed.aal4649

Building a better basement membrane

The most common form of congenital muscular dystrophy is caused by mutations in the gene encoding one chain of laminin-211, a basement membrane component. Deleterious muscle function results from the unstable basement membrane and lack of proper connections to the muscle plasma membrane, leading to muscle degeneration. Using a transgenic mouse model of muscular dystrophy, Reinhard et al. studied whether linker proteins could be used to fortify the basement membrane, using laminin-411 as a scaffold. Transgenic mice expressing two linker proteins—a shorter form of agrin and the fusion protein αLNNd, composed of parts of laminin-α1 and nidogen-1—had stable basement membranes, improved muscle function, and prolonged life spans. These proteins could be a missing link for muscular dystrophy therapy.

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