Human Molecular Genetics Advance Access originally published online on February 2, 2005
Human Molecular Genetics 2005 14(6):775-783; doi:10.1093/hmg/ddi072
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Human Molecular Genetics, Vol. 14, No. 6 © Oxford University Press 2005; all rights reserved
-Sarcoglycan compensates for lack of 
-sarcoglycan in a mouse model of limb-girdle muscular dystrophy
1Department of Molecular Therapy, National Institute of Neuroscience, NCNP, 4-1-1 Ogawahigashi-cho, Kodaira, Tokyo 187-8502, Japan, 2Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan and 3The Burnham Institute, La Jolla, CA 92037, USA
* To whom correspondence should be addressed. Tel: +81 423461720; Fax: +81 423461750; Email: imamura{at}ncnp.go.jp
Received October 18, 2004; Accepted January 24, 2005
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 (SG) subcomplex, which is composed of 
-, ß-, 
- and 
-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 homolog 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 the overexpression of -SG may represent a therapeutic strategy for treatment of LGMD 2D.
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