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Direct Transfer of Human Dystrophin Genes into Striated Muscles of MDX Mice

Plasmid DNA constructs containing either a human full length dystrophin cDNA (G. Dickson, London, UK) or a deleted, Becker type, dystrophin cDNA (K.E.Davies, DR. Love, Oxford, UK.) were injected into hearts and quadriceps of dystrophin deficient MDX mice. Seven days later, analysis of immunohistochemical staining for dystrophin showed expression of dystrophin proteins in ∼1 % of quadriceps muscle cells localized mostly in the sarcolemma. 10-15 dystrophin positive cardiocyte were also seen in sections of injected hearts. Western-blot of quadriceps muscles has also identified the dystrophin expressions. Peripherally localized nuclei of muscle cells were shown in about 50 percent of dystrophin positive myofibers compared with 20 percent of dystrophin negativ myofibers suggesting the the functional effect of expressed human dystrophin protein. This direct gene transfer method has an alternative application for genetherapy of inherited myopathies but the efficiency must be increased.