Title: In vivo analysis of dystrophin (re-) expression in DmdEGFP and DmdEGFP-mdx reporter mice
Abstract: Duchenne muscular dystrophy (DMD), the most frequently inherited muscle disease in childhood, is caused by mutations in the gene encoding dystrophin. The modification of dystrophin mRNA splicing, called exon-skipping, is a promising therapeutic strategy. This approach uses small molecules, anti-sense oligonucleotides, that “repair” the open reading frame of the Dmd gene through skipping of exons, which flank the original mutation and lead to the production of truncated dystrophin. Animal models play an indispensable role in the development and optimization of therapeutic approaches for DMD as well as in understanding the role dystrophin in the muscle. Our group recently generated the first dystrophin reporter mice on the wildtype (DmdEGFP) and mdx (DmdEGFP-mdx) genetic background. These models express an endogenous dystrophin-EGFP fusion protein permitting the visualization of dystrophin expression using native fluorescence. We currently study the expression of dystrophin in vivo using intravital two photon microscopy in skeletal muscle from DmdEGFP mice. We analyze the dynamics of dystrophin during the course of an acute injury and reconstitute the regenerating muscle in 3D using the dystrophin-EGFP re-expression in myofibers. We use DmdEGFP-mdx and study in vivo the restoration of dystrophin following of exon skipping for direct visualization, quantification and precising the dynamics of dystrophin restoration. Data of these ongoing experiments will improve our understanding of the pharmacodynamics of exon skipping strategies.
Publication Year: 2017
Publication Date: 2017-09-12
Language: en
Type: article
Indexed In: ['crossref']
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