Transgenic expression of alpha 7 beta 1 integrin maintains muscle integrity, increases regenerative capacity, promotes hypertrophy, and reduces cardiomyopathy in dystrophic mice

We previously reported that enhanced expression of the alpha7beta1 integrin ameliorates the development of muscular dystrophy and extends longevity in alpha7BX2mdx/utr(-/-) transgenic mice (Burkin DJ, Wallace GQ, Nicol KJ, Kaufman DJ, Kaufman SJ: Enhanced expression of the alpha7beta1 integrin reduces muscular dystrophy and restores viability in dystrophic mice. J Cell Biol 2001, 152:1207-1218). We now report on the mechanism by which these mice were rescued by the integrin. As a result of increased integrin in alpha7BX2-mdx/utr(-/-) mice the structural integrity of the myotendinous and neuromuscular junctions are maintained. A twofold increase in satellite cells in alpha7BX2-mdx/utr(-/-) skeletal muscle was detected by immunofluorescence using the satellite cell marker c-met. These cells enhanced the regenerative capacity of muscle in the transgenic animals as determined by fusion of BrdUrd-labeled cells into muscle fibers. Increased integrin also leads to hypertrophy. Finally, transgenic expression of alpha7BX2 integrin chain in skeletal muscle secondarily reduces the development of cardiomyopathy, the ultimate cause of death in these animals. We believe this multiplicity of responses to increased alpha7beta1 integrin collectively inhibits the development of muscle disease and increases longevity in these mice.