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Expression of deletion-containing dystrophins in mdx muscle: implications for gene therapy and dystrophin function. Pediatr Res 1995 Jun;37(6):693-700

Date

06/01/1995

Pubmed ID

7651751

DOI

10.1203/00006450-199506000-00004

Abstract

The expression of full-length dystrophin and various dystrophin deletion mutants was monitored in mdx mouse muscle after intramuscular injection of dystrophin-encoding plasmid DNAs. Recombinant dystrophin proteins, including those lacking either the amino terminus, carboxyl terminus, or most of the central rod domain, showed localization to the plasma membrane. This suggests that there are multiple attachment sites for dystrophin to the plasma membrane. Only those constructs containing the carboxyl terminus were able to stabilize dystrophin-associated proteins (DAP) at the membrane, consistent with other studies that suggest that this domain is critical to DAP binding. Colocalization with DAP was not necessary for membrane localization of the various dystrophin molecules. However, stabilization and co-localization of the DAP did seem to be a prerequisite for expression and/or stabilization of mutant dystrophins beyond 1 wk and these same criteria seemed important for mitigating the histopathological consequences of dystrophin deficiency.

Author List

Fritz JD, Danko I, Roberds SL, Campbell KP, Latendresse JS, Wolff JA

Author

Jeffery Duane Fritz PhD Associate Professor in the Medical School Regional Campuses department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Base Sequence
Dystrophin
Gene Deletion
Genetic Therapy
Injections, Intramuscular
Mice
Mice, Inbred mdx
Molecular Sequence Data
Muscular Dystrophy, Animal
Plasmids