The dystrophin-glycoprotein complex maintains the integrity of skeletal muscle by associating laminin in the extracellular matrix with the actin cytoskeleton. Several human muscular dystrophies arise from defects in components of this complex. The 71 integrin also binds laminin and links the extracellular matrix with the cytoskeleton. Enhancement of 7 integrin levels alleviates pathology in mdx/utrn-/- mice, a model of Duchenne muscular dystrophy, and thus the integrin may functionally compensate for the absence of dystrophin. To test if increasing 7 integrin levels affects transcription and cellular functions, we generated 7 integrin inducible C2C12 cells and transgenic mice that over-express the integrin in skeletal muscle. C2C12 myoblasts with elevated levels of integrin exhibited increased adhesion to laminin, faster proliferation when serum was limited, resistance to staurosporine-induced apoptosis, and normal differentiation. Transgenic expression of 8-fold more integrin in skeletal muscle did not result in notable toxic effects in vivo. Moreover, high levels of 7 integrin in both myoblasts and in skeletal muscle did not disrupt global gene expression profiles. Thus increasing integrin levels can compensate for defects in the extracellular matrix and cytoskeleton linkage caused by compromises in the dystrophin-glycoprotein complex without triggering apparent overt negative side effects. These results support utilizing integrin enhancement as a therapy for muscular dystrophy.