Human Molecular Genetics Advance Access published online on February 2, 2005
Human Molecular Genetics, doi:10.1093/hmg/ddi072
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1 Department of Molecular Therapy, National Institute of Neuroscience, NCNP, 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8502, Japan
* To whom correspondence should be addressed. Dystrophin and the dystrophin-associated protein (DAP) complex protect the sarcolemma against contraction-induced injury and serve as a mechanical link between the extracellular matrix and the actin cytoskeleton. Some of the functional properties of the DAP complex are mediated by its sarcoglycan subcomplex, which is composed of
Article
-Sarcoglycan compensates for lack of 
-sarcoglycan in a mouse model of limb girdle muscular dystrophy
2 Department of Molecular Therapy, National Institute of Neuroscience, NCNP, 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8502, Japan; Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan
3 The Burnham Institute, La Jolla, California 92037, USA
Michihiro Imamura, E-mail: imamura{at}ncnp.go.jp
Abstract 
-, 
-, 
- and 
-sarcoglycans (SGs). Autosomal recessive limb-girdle muscular dystrophy type-2D (LGMD 2D) results from reduction in SG subcomplex levels caused by specific mutations in the muscle-specific -SG gene. 
-SG is a widely expressed homologue of the muscle-specific -SG, and expression of -SG may compensate for the pathologic changes in -SG function. Thus, the goal of the present study was to investigate whether overexpression of -SG can compensate for dysfunction of -SG. Several transgenic mouse lines that overexpress -SG in skeletal muscle were established. Overexpression of -SG in normal mice resulted in substitution of -SG for -SG in the SG complex of skeletal muscle without any obvious abnormalities. To determine whether an increase in -SG expression may prevent muscular dystrophy in the context of -SG-deficiency, these -SG transgenic mice were crossed with -SG-deficient mice. -SG-deficient mice overexpressing -SG exhibited no skeletal muscle cell membrane damage or abnormal contraction. These data suggest that overexpression of -SG may represent a therapeutic strategy for treatment of LGMD 2D.
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