Morpholino knockdown of lysyl oxidase impairs zebrafish development, and reflects some aspects of copper metabolism disorders.
Lysyl oxidase (LOX), a copper-dependent amine oxidase known in mammals to catalyze the cross-linking of collagen and elastin in the extracellular matrix, is a member of a multigenic family. Eight genes encoding lysyl oxidase isoforms have been identified in zebrafish. Recent studies have revealed a critical role for two zebrafish lysyl oxidases-like in the formation of the notochord. We now present the role of Lox in zebrafish development. lox morpholino-mediated knockdown results in a mildly undulated notochord, truncated anterior-posterior axis, tail bending and smaller head. Analyses of morphants show a complete disorganization of muscle somites and neural defects, in accordance with the lox expression pattern. Lox inhibition also induces pigment defects and pharyngeal arch deformities consistent with neural crest dysfunction. Taken together, these data reveal a role for Lox in early morphogenesis, especially in muscle development and neurogenesis, and resume some aspects of physiopathology of copper metabolism.
Reynaud
Caroline
C
IBCP, Institut de Biologie et Chimie des Protéines, Lyon, France. c.reynaud@ibcp.fr
Baas
Dominique
D
Gleyzal
Claudine
C
Le Guellec
Dominique
D
Sommer
Pascal
P
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003300:Copper / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D008659:Metabolic Diseases / Q000201:enzymology*; D008969:Molecular Sequence Data; D009432:Neural Crest / Q000166:cytology; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism*; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D015027:Zebrafish / Q000033:anatomy & histology / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*
D016376:Oligonucleotides, Antisense; D003300:Copper; D008249:Protein-Lysine 6-Oxidase