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 overexpress ing dystrophin 50-fold) mice were transplanted into dystrophin-deficie nt mdx mouse muscles. Four weeks after transplantation, dystrophin-pos itive fibers were observed four times more frequently in cross section s of muscles injected with Tg-MDA. Myoblasts from Tg-MDA mice also exp ressing the beta-gal transgene (Tg-MDA/beta-gal) and myoblasts from be ta-gal transgenic mice containing one normal dystrophin gene (normal/b eta-gal) were also transplanted into mdx mouse muscles. Four weeks aft er transplantation, the fiber length positive for dystrophin (nuclear domain) was shorter (439 +/- 326 mu m) than the beta-gal nuclear domai n (1466 +/- 713 mu m) of the same fiber when normal/beta-gal myoblasts were transplanted, but increased (1302 +/- 487 mu m) when Tg-MDA/beta -gal myoblasts were used. These experiments show that despite the pres ence in Tg-MDA myoblasts of constructions which lead in vivo in transg enic mice to an overexpression of dystrophin 50-fold, the membrane are a over which dystrophin was expressed was increased only threefold. Th is observation is also expected for vector-mediated gene therapy. (C) 1998 John Wiley & Sons, Inc.