δ-Sarcoglycan is required for early zebrafish muscle organization

Mutations in sarcoglycans (α-, β-, γ-, and δ-) have been linked with limb girdle muscular dystrophy (LGMD) types 2C–F in humans. We have cloned the zebrafish orthologue encoding δ-sarcoglycan and mapped the gene to linkage group 21. The predicted zebrafish δ-sarcoglycan protein is highly homologous...

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Bibliographic Details
Published in:Experimental cell research 2005-03, Vol.304 (1), p.105-115
Main Authors: Guyon, Jeffrey R., Mosley, Alycia N., Jun, Susan J., Montanaro, Federica, Steffen, Leta S., Zhou, Yi, Nigro, Vincenzo, Zon, Len I., Kunkel, Louis M.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Base Sequence
Cloning, Molecular
DAPC
Down-Regulation
Dystrophin - metabolism
Humans
Limb girdle muscular dystrophy
Mice
Molecular Sequence Data
Muscle, Skeletal - cytology
Muscle, Skeletal - embryology
Muscular dystrophy
Myosepta
Sarcoglycan
Sarcoglycans - analysis
Sarcoglycans - genetics
Sarcoglycans - physiology
Sarcolemma - chemistry
Sarcolemmal membrane
Zebrafish
Zebrafish - embryology
Zebrafish Proteins - genetics
Zebrafish Proteins - physiology
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Summary:Mutations in sarcoglycans (α-, β-, γ-, and δ-) have been linked with limb girdle muscular dystrophy (LGMD) types 2C–F in humans. We have cloned the zebrafish orthologue encoding δ-sarcoglycan and mapped the gene to linkage group 21. The predicted zebrafish δ-sarcoglycan protein is highly homologous with its human orthologue including conservation of two of the three predicted glycosylation sites. Like other members of the dystrophin-associated protein complex (DAPC), δ-sarcoglycan localizes to the sarcolemmal membrane of the myofiber in adult zebrafish, but is more apparent at the myosepta in developing embryos. Zebrafish embryos injected with morpholinos against δ-sarcoglycan were relatively inactive at 5 dpf, their myofibers were disorganized, and swim bladders uninflated. Immunohistochemical and immunoblotting experiments show that δ-, β-, and γ-sarcoglycans were all downregulated in the morphants, whereas dystrophin expression was unaffected. Whereas humans lacking δ-sarcoglycan primarily show adult phenotypes, our results suggest that δ-sarcoglycan plays a role in early zebrafish muscle development.
ISSN:0014-4827
1090-2422
DOI:10.1016/j.yexcr.2004.10.032