title: A novel early onset phenotype in a zebrafish model of merosin deficient congenital muscular dystrophy.
abstract: Merosin deficient congenital muscular dystrophy (MDC1A) is a severe neuromuscular disorder with onset in infancy that is associated with severe morbidities (particularly wheelchair dependence) and early mortality. It is caused by recessive mutations in the LAMA2 gene that encodes a subunit of the extracellular matrix protein laminin 211. At present, there are no treatments for this disabling disease. The zebrafish has emerged as a powerful model system for the identification of novel therapies. However, drug discovery in the zebrafish is largely dependent on the identification of phenotypes suitable for chemical screening. Our goal in this study was to elucidate novel, early onset abnormalities in the candyfloss (caf) zebrafish, a model of MDC1A. We uncovered and characterize abnormalities in spontaneous coiling, the earliest motor movement in the zebrafish, as a fully penetrant change specific to caf mutants that is ideal for future drug testing.
authors.affiliation: Departments of Pediatrics and Molecular Genetics, University of Toronto, Toronto, Canada.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Smith
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA United States of America.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Wang
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA United States of America.
authors.forename: Vandana A
authors.initials: VA
authors.lastname: Gupta
authors.affiliation: Departments of Pediatrics and Molecular Genetics, University of Toronto, Toronto, Canada.|Division of Neurology and Program for Genetics and Genome Biology, Hospital for Sick Children, Toronto, Canada.
authors.forename: James J
authors.initials: JJ
authors.lastname: Dowling
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D006579:Heterozygote; D007797:Laminin / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009136:Muscular Dystrophies / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010590:Phalloidine / Q000096:biosynthesis; D010641:Phenotype; D015027:Zebrafish / Q000378:metabolism
chemical_list: D007797:Laminin; C520014:laminin alpha2, zebrafish; D010590:Phalloidine