Up-regulation of utrophin, a homolog of dystrophin, is known to ameliorate the dystrophic phenotype in animal models of Duchenne muscular dystrophy. We have previously demonstrated that the active form of RhoA (RhoAV14) increases the expression of utrophin and its localization at the plasma membrane in cultured myoblasts. In this paper, we ask whether RhoAV14 can up-regulate utrophin also in mice. A plasmid encoding for RhoAV14 was injected into skeletal muscles followed by electroporation. Muscles expressing RhoAV14 were analyzed by Western-immunoblotting, real time PCR amplification and immunohistochemistry. We found that RhoAV14 increased utrophin protein expression and distribution specifically at the plasma membrane in muscle fibers without any effect on utrophin transcription. Utrophin up-regulation, uncoupled from that of its mRNA, has been previously observed in pathological processes and in normal regenerating conditions. (C) 2009 Elsevier Inc. All rights reserved.