Transplantation of myoblasts from a transgenic mouse overexpressing dystrophin produced only a relatively small increase of dystrophin-positive membrane

Myoblast cultures from normal and Tg-MDA (transgenic mouse overexpressing dystrophin 50-fold) mice were transplanted into dystrophin-deficient mdx mouse muscles. Four weeks after transplantation, dystrophin-positive fibers were observed four times more frequently in cross sections of muscles injected with Tg-MDA. Myoblasts from Tg-MDA mice also expressing the beta-gal transgene (Tg-MDA/beta-gal) and myoblasts from beta-gal transgenic mice containing one normal dystrophin gene (normal/beta-gal) were also transplanted into mdx mouse muscles. Four weeks after transplantation, the fiber length positive for dystrophin (nuclear domain) was shorter (439 +/- 326 microm) than the beta-gal nuclear domain (1466 +/- 713 microm) of the same fiber when normal/beta-gal myoblasts were transplanted, but increased (1302 +/- 487 microm) when Tg-MDA/beta-gal myoblasts were used. These experiments show that despite the presence in Tg-MDA myoblasts of constructions which lead in vivo in transgenic mice to an overexpression of dystrophin 50-fold, the membrane area over which dystrophin was expressed was increased only threefold. This observation is also expected for vector-mediated gene therapy.