title: The dystrophin associated protein complex in zebrafish.
abstract: Many cases of muscular dystrophy in humans are caused by mutations in members of the dystrophin associated protein complex (DAPC). Zebrafish are small vertebrates whose bodies are composed predominantly of skeletal muscle, making them attractive models for studying mammalian muscle disorders. Potential orthologs to most of the human DAPC proteins have been found in zebrafish by database screening. Expression of the sarcoglycans, dystroglycan and dystrophin has been confirmed by western blotting. Immunohistochemical and biochemical techniques localize these proteins to the muscle cell membrane in adult zebrafish. Morpholino (MO) experiments designed to inhibit the translation of dystrophin mRNA produce juvenile zebrafish that are less active than zebrafish injected with control morpholinos. Western blot analysis of the dystrophin morpholino-injected zebrafish shows concurrent reduction of dystrophin and the sarcoglycans, suggesting that these proteins, like those in mammals, are part of a complex whose integrity is dependent on dystrophin expression. These results indicate that the zebrafish is an excellent animal model in which to approach the study of dystrophin and its associated proteins.
authors.affiliation: Division of Genetics, Children's Hospital, Boston, MA 02115, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Guyon
authors.forename: A N
authors.initials: AN
authors.lastname: Mosley
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.forename: K F
authors.initials: KF
authors.lastname: O'Brien
authors.forename: X
authors.initials: X
authors.lastname: Sheng
authors.forename: K
authors.initials: K
authors.lastname: Chiang
authors.forename: A J
authors.initials: AJ
authors.lastname: Davidson
authors.forename: J M
authors.initials: JM
authors.lastname: Volinski
authors.forename: L I
authors.initials: LI
authors.lastname: Zon
authors.forename: L M
authors.initials: LM
authors.lastname: Kunkel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D019992:Databases as Topic; D016189:Dystrophin / Q000096:biosynthesis* / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D005091:Exons; D015723:Gene Library; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008957:Models, Genetic; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D010641:Phenotype; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D017386:Sequence Homology, Amino Acid; D015027:Zebrafish
chemical_list: D018076:DNA, Complementary; D016189:Dystrophin