Journal article
Molecular Pathogenesis of Muscle Degeneration in the δ-Sarcoglycan-Deficient Hamster
The American journal of pathology, Vol.153(5), pp.1623-1630
11/1998
DOI: 10.1016/S0002-9440(10)65751-3
PMCID: PMC1853419
PMID: 9811355
Abstract
The BIO14.6 hamster is an extensively used animal model of autosomal recessive cardiomyopathy and muscular dystrophy. Recently, a large deletion in the 5′ end of the δ-sarcoglycan gene was found to be the primary genetic defect in the hamster. In the present investigation, we studied the effects of the δ-sarcoglycan deletion on transcription, expression, and function of the dystrophin-glycoprotein complex in skeletal and cardiac muscle. We demonstrated that in striated muscle the genetic defect leads to the complete deficiency of δ-sarcoglycan and a concomitant loss of α-, β-, and γ-sarcoglycan. In addition, absence of the sarcoglycan complex reduced the expression of α-dystroglycan in striated muscle fibers. These findings indicated that the primary defect in the BIO14.6 hamster leads to the dissociation of the dystroglycan complex from the sarcoglycan complex and disrupted anchorage of α-dystroglycan to the cell surface. Using intravenous injection of Evans blue dye as an
in vivo
tracer assay, we demonstrated that perturbation of the dystrophin-glycoprotein complex caused extensive fiber damage in skeletal and cardiac muscle of the BIO14.6 hamster. Based on our results, we propose that loss of δ-sarcoglycan results in the impairment of sarcolemmal integrity, finally leading to muscular dystrophy and cardiomyopathy.
Details
- Title: Subtitle
- Molecular Pathogenesis of Muscle Degeneration in the δ-Sarcoglycan-Deficient Hamster
- Creators
- Volker Straub - From the Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, University of Iowa College of Medicine, Iowa City, IowaFranck Duclos - From the Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, University of Iowa College of Medicine, Iowa City, IowaDavid P Venzke - From the Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, University of Iowa College of Medicine, Iowa City, IowaJane C Lee - From the Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, University of Iowa College of Medicine, Iowa City, IowaSusan Cutshall - From the Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, University of Iowa College of Medicine, Iowa City, IowaCynthia J Leveille - From the Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, University of Iowa College of Medicine, Iowa City, IowaKevin P Campbell - From the Howard Hughes Medical Institute, Department of Physiology and Biophysics and Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- The American journal of pathology, Vol.153(5), pp.1623-1630
- DOI
- 10.1016/S0002-9440(10)65751-3
- PMID
- 9811355
- PMCID
- PMC1853419
- NLM abbreviation
- Am J Pathol
- ISSN
- 0002-9440
- eISSN
- 1525-2191
- Publisher
- American Society for Investigative Pathology
- Language
- English
- Date published
- 11/1998
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Obstetrics and Gynecology
- Record Identifier
- 9984068381702771
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