title: Delta-sarcoglycan is required for early zebrafish muscle organization.
abstract: Mutations in sarcoglycans (alpha-, beta-, gamma-, and delta-) have been linked with limb girdle muscular dystrophy (LGMD) types 2C-F in humans. We have cloned the zebrafish orthologue encoding delta-sarcoglycan and mapped the gene to linkage group 21. The predicted zebrafish delta-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), delta-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 delta-sarcoglycan were relatively inactive at 5 dpf, their myofibers were disorganized, and swim bladders uninflated. Immunohistochemical and immunoblotting experiments show that delta-, beta-, and gamma-sarcoglycans were all downregulated in the morphants, whereas dystrophin expression was unaffected. Whereas humans lacking delta-sarcoglycan primarily show adult phenotypes, our results suggest that delta-sarcoglycan plays a role in early zebrafish muscle development.
authors.affiliation: Division of Genetics and Hematology/Oncology, Children's Hospital Boston, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Guyon
authors.forename: Alycia N
authors.initials: AN
authors.lastname: Mosley
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Jun
authors.forename: Federica
authors.initials: F
authors.lastname: Montanaro
authors.forename: Leta S
authors.initials: LS
authors.lastname: Steffen
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Nigro
authors.forename: Len I
authors.initials: LI
authors.lastname: Zon
authors.forename: Louis M
authors.initials: LM
authors.lastname: Kunkel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D015536:Down-Regulation; D016189:Dystrophin / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology*; D049031:Sarcoglycans / Q000032:analysis / Q000235:genetics* / Q000502:physiology*; D012508:Sarcolemma / Q000737:chemistry; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000235:genetics* / Q000502:physiology*
chemical_list: D016189:Dystrophin; D049031:Sarcoglycans; D029961:Zebrafish Proteins