Cells adhere to their extracellular matrix by way of integrins, transmembrane molecules that attach the cytoskeleton to the extracellular basement membrane (one kind of extracellular matrix). In some muscular dystrophies, specific integrins are disrupted and muscle fibers detach from the myotendenous junction and degenerate. This integrin disruption causes a constant cycle of regeneration and degeneration, which greatly harms the tissue over time. Congenital muscular dystrophy affects the integrin alpha 7 gene and prevents the muscle cell from producing the affiliated protein. In an attempt to rescue integrin alpha 7 dystrophies, this project over-expressed another integrin, integrin alpha 6, in zebrafish (Danio rerio). Preliminary data suggest it is possible to prevent fiber detachments in muscle, a characteristic of dystrophy, by over-expressing integrin alpha 6 in zebrafish lacking integrin alpha 7. Furthermore, a limited number of embryos, with both integrin alpha 7 and dystroglycan 1 deficiencies, show improved muscle structure when over-expressing the integrin alpha 6 protein. The integrin alpha 6 protein may hold promise for gene therapy applications because it already exists within the muscle fibers, reducing the risk of immunorejection. This protein may serve a useful therapeutic purpose if it can be both expressed uniformly and effectively in human skeletal muscle.
McGlauflin, Rose E., "Altered Integrin Alpha 6 Expression As A Rescue For Muscle Fiber Detachment In Zebrafish (Danio Rerio)" (2014). Honors College. 140.