Mini- and full-length dystrophin gene transfer induces the recovery of nitric oxide synthase at the sarcolemma of mdx4cv skeletal muscle fibers

Gene Therapy
A DecrouyB J Jasmin

Abstract

In normal skeletal muscle fibers, dystrophin accumulates at the cytoplasmic face of the sarcolemma where it associates with dystrophin-associated proteins (DAPs). Several studies have recently shown that the neuronal isoform of nitric oxide synthase (nNOS) is also located at the sarcolemma, and that this membrane localization is mediated through interactions of nNOS with one of the DAPs, namely alpha 1-syntrophin. Since the lack of dystrophin in muscle fibers from Duchenne muscular dystrophy patients and mdx mice is accompanied by an absence of sarcolemmal nNOS, we examined in the present study, whether dystrophin gene replacement would lead to the restoration of nNOS at its appropriate subcellular location. To this end, tibialis anterior muscles from mdx4cv mice were directly injected with plasmid DNA encoding either full-length (pRSV-dys) or mini-(pRSV-dyB; lacking exons 17-48) dystrophin. For these experiments, we chose to study 10-week-old mdx4cv mice since at this developmental stage, muscles from these mice have already undergone several cycles of degeneration-regeneration. Immunofluorescence experiments performed on serial cross-sections revealed that approximately 50% of the dystrophin-positive fibers also exhibited sig...Continue Reading

Citations

Sep 11, 2002·Neuromuscular Disorders : NMD·Dominic J Wells, Kim E Wells
Jul 10, 2003·Lancet Neurology·Robert KapsaEdward Byrne
Aug 31, 2001·The American Journal of Chinese Medicine·S S ChenS L Yang
Dec 18, 2001·Microscopy Research and Technique·D Blottner, G Lück
Feb 24, 2006·Journal of Muscle Research and Cell Motility·Romesh A DraviamSimon C Watkins
Dec 18, 2001·Microscopy Research and Technique·Y Miyagoe-Suzuki, S I Takeda
Aug 10, 2006·Journal of Muscle Research and Cell Motility·Bruno ConstantinChristian Cognard
Oct 1, 1998·Italian Journal of Neurological Sciences·G L LenziV Di Piero
Apr 26, 2003·Journal of Hypertension·Ekaterina KintsurashviliHaralambos Gavras
Oct 29, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·A VandebrouckB Constantin
Jan 12, 2001·Physiological Reviews·J S Stamler, G Meissner

❮ Previous
Next ❯

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.