AMELIORATION OF THE DYSTROPHIC PHENOTYPE OF MDX MICE USING A TRUNCATED UTROPHIN TRANSGENE

DUCHENNE muscular dystrophy (DMD) is a severe, progressive muscle-wast ing disease that causes cardiac or respiratory failure(1,2) and result s in death at about 20 years of age, Replacement of the missing protei n, dystrophin, using myoblast transfer in humans or viral/liposomal de livery in the mouse DMD model is inefficient and short-lived(3,4). One alternative approach to treatment would be to upregulate the closely related protein, utrophin(5,6), which might be able to compensate for the dystrophin deficiency in all relevant muscles(7,8). As a first ste p to this approach, we have expressed a utrophin transgene at high lev els in the dystrophin-deficient mdx mouse. Our results indicate that h igh expression of the utrophin transgene in skeletal and diaphragm mus cle can markedly reduce the dystrophic pathology. These data suggest t hat systemic upregulation of utrophin in DMD patients may lead to the development of an effective treatment for this devastating disorder.