TETRACYCLINE-REGULATED GENE-EXPRESSION FOLLOWING DIRECT GENE-TRANSFERINTO MOUSE SKELETAL-MUSCLE

For most experimental and therapeutic applications of gene transfer, r egulation of the timing and level ofgene expression is preferable to c onstitutive gene expression. Among the systems that have been develope d for pharmacologically controlled gene expression in mammalian cells, the bacterial tetracycline (tet)-responsive system has the advantage that it is dependent on a drug (tet) that is both highly specific and non-toxic. The tet-responsive system has been previously used to modul ate expression of cell cycle regulatory proteins in cultured cells, re porter genes in plants and transgenic mice and reporter genes directly injected into the heart. Here we show that orally or parenterally adm inistered tet regulates expression of tet-responsive plasmids injected directly into mouse skeletal muscle. Reporter gene expression was sup pressed by two orders of magnitude in the presence of tet, and that su ppression was reversed when tet was withdrawn. These data show that sk eletal muscle offers an accessible and well characterized target tissu e for tet-controlled expression of genes in vivo, suggesting applicati ons to developmental studies and gene therapy.