Journal article
Progressive Muscular Dystrophy in α-Sarcoglycan–deficient Mice
The Journal of cell biology, Vol.142(6), pp.1461-1471
09/21/1998
DOI: 10.1083/jcb.142.6.1461
PMCID: PMC2141773
PMID: 9744877
Abstract
Limb-girdle muscular dystrophy type 2D (LGMD 2D) is an autosomal recessive disorder caused by mutations in the α-sarcoglycan gene. To determine how α-sarcoglycan deficiency leads to muscle fiber degeneration, we generated and analyzed α-sarcoglycan– deficient mice. Sgca-null mice developed progressive muscular dystrophy and, in contrast to other animal models for muscular dystrophy, showed ongoing muscle necrosis with age, a hallmark of the human disease. Sgca-null mice also revealed loss of sarcolemmal integrity, elevated serum levels of muscle enzymes, increased muscle masses, and changes in the generation of absolute force. Molecular analysis of Sgca-null mice demonstrated that the absence of α-sarcoglycan resulted in the complete loss of the sarcoglycan complex, sarcospan, and a disruption of α-dystroglycan association with membranes. In contrast, no change in the expression of ε-sarcoglycan (α-sarcoglycan homologue) was observed. Recombinant α-sarcoglycan adenovirus injection into Sgca-deficient muscles restored the sarcoglycan complex and sarcospan to the membrane. We propose that the sarcoglycan–sarcospan complex is requisite for stable association of α-dystroglycan with the sarcolemma. The Sgca-deficient mice will be a valuable model for elucidating the pathogenesis of sarcoglycan deficient limb-girdle muscular dystrophies and for the development of therapeutic strategies for this disease.
Details
- Title: Subtitle
- Progressive Muscular Dystrophy in α-Sarcoglycan–deficient Mice
- Creators
- Franck Duclos - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa 52242-1101; Department of Pathology and Department of Obstetrics and Gynecology, University of Iowa College of Medicine, Iowa City, Iowa 52242; Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MisVolker Straub - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa 52242-1101; Department of Pathology and Department of Obstetrics and Gynecology, University of Iowa College of Medicine, Iowa City, Iowa 52242; Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MisSteven A Moore - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa 52242-1101; Department of Pathology and Department of Obstetrics and Gynecology, University of Iowa College of Medicine, Iowa City, Iowa 52242; Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MisDavid P Venzke - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa 52242-1101; Department of Pathology and Department of Obstetrics and Gynecology, University of Iowa College of Medicine, Iowa City, Iowa 52242; Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MisRon F Hrstka - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa 52242-1101; Department of Pathology and Department of Obstetrics and Gynecology, University of Iowa College of Medicine, Iowa City, Iowa 52242; Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MisRachelle H Crosbie - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa 52242-1101; Department of Pathology and Department of Obstetrics and Gynecology, University of Iowa College of Medicine, Iowa City, Iowa 52242; Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MisMadeleine Durbeej - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa 52242-1101; Department of Pathology and Department of Obstetrics and Gynecology, University of Iowa College of Medicine, Iowa City, Iowa 52242; Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MisConnie S Lebakken - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa 52242-1101; Department of Pathology and Department of Obstetrics and Gynecology, University of Iowa College of Medicine, Iowa City, Iowa 52242; Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MisAudrey J Ettinger - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa 52242-1101; Department of Pathology and Department of Obstetrics and Gynecology, University of Iowa College of Medicine, Iowa City, Iowa 52242; Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MisJack van der Meulen - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa 52242-1101; Department of Pathology and Department of Obstetrics and Gynecology, University of Iowa College of Medicine, Iowa City, Iowa 52242; Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MisKathleen H Holt - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa 52242-1101; Department of Pathology and Department of Obstetrics and Gynecology, University of Iowa College of Medicine, Iowa City, Iowa 52242; Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MisLeland E Lim - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa 52242-1101; Department of Pathology and Department of Obstetrics and Gynecology, University of Iowa College of Medicine, Iowa City, Iowa 52242; Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MisJoshua R Sanes - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa 52242-1101; Department of Pathology and Department of Obstetrics and Gynecology, University of Iowa College of Medicine, Iowa City, Iowa 52242; Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MisBeverly L Davidson - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa 52242-1101; Department of Pathology and Department of Obstetrics and Gynecology, University of Iowa College of Medicine, Iowa City, Iowa 52242; Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MisJohn A Faulkner - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa 52242-1101; Department of Pathology and Department of Obstetrics and Gynecology, University of Iowa College of Medicine, Iowa City, Iowa 52242; Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MisRoger Williamson - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa 52242-1101; Department of Pathology and Department of Obstetrics and Gynecology, University of Iowa College of Medicine, Iowa City, Iowa 52242; Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MisKevin P Campbell - Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa 52242-1101; Department of Pathology and Department of Obstetrics and Gynecology, University of Iowa College of Medicine, Iowa City, Iowa 52242; Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Mis
- Resource Type
- Journal article
- Publication Details
- The Journal of cell biology, Vol.142(6), pp.1461-1471
- DOI
- 10.1083/jcb.142.6.1461
- PMID
- 9744877
- PMCID
- PMC2141773
- ISSN
- 0021-9525
- eISSN
- 1540-8140
- Language
- English
- Date published
- 09/21/1998
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pathology; Iowa Neuroscience Institute; Obstetrics and Gynecology
- Record Identifier
- 9984047673802771
Metrics
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