Organization of the myotendinous junction is dependent on the presence of alpha 7 beta 1 integrin

The laminin receptor alpha 7 beta 1 is enriched at the myotendinous junctio ns, and mice with a targeted inactivation of the alpha 7 gene develop a for m of muscular dystrophy that primarily affects this structure. By ultrastru ctural analysis of alpha 7-deficient mice, in comparison with wild-type and mdx mice, we attempted to elucidate the role of alpha 7 integrin for the i ntegrity and function of the myotendinous junctions. Ultrastructurally, myo tendinous junctions of alpha 7-deficient myofibers lose their interdigitati ons and the myofilaments retract from the sarcolemmal membrane, whereas the lateral side of the myofibers remains morphologically normal. The basement membrane at the myotendinous junctions in alpha 7 -/- mice is significantl y broadened, and immunogold-histochemistry has demonstrated that the lamini n alpha 2 chain is not localized here but, instead, in the matrix of the ne ighboring tendon. In contrast, mdx mice have normal myotendinous junctions, with a matrix protein pattern also found in wild-type mice, however the la teral sides of the myofibers are severely damaged. These results suggest th at the alpha 7 beta 1 integrin is a major receptor connecting the muscle ce ll to the tendon and helps to organize the myotendinous junction, whereas t he dystrophin-glycoprotein complex is necessary for the lateral integrity o f the muscle cell.