Non-toxic ubiquitous over-expression of utrophin in the mdx mouse

Duchenne muscular dystrophy (DMD) is an inherited, severe muscle wasting di sease caused by the loss of the cytoskeletal protein, dystrophin. Patients usually die in their late teens or early twenties of cardiac or respiratory failure. We have previously demonstrated that the dystrophin related prote in, utrophin is able to compensate for the loss of dystrophin in the mdx mo use, the mouse model of the disease. Expression of a utrophin transgene und er the control of an HSA promoter results in localization of utrophin to th e sarcolemma and prevents the muscle pathology. Here we show that the over- expression of full-length utrophin in a broad range of tissues is not detri mental in the mdx mouse. These findings have important implications for the feasibility of the up-regulation of utrophin in therapy for DMD since they suggest that tissue specific up-regulation may not be necessary. (C) 2001 Elsevier Science B.V. All rights reserved.