Essential role for the alpha 1 chain of type VIII collagen in Zebrafish notochord formation

Several zebrafish mutants identified in large‐scale forward genetic screens exhibit notochord distortion. We now report the cloning and further characterization of one such mutant, gulliverm208 (gulm208). The notochord defect in gulm208 mutants is exacerbated under conditions of copper depletion or...

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Bibliographic Details
Published in:Developmental dynamics 2008-12, Vol.237 (12), p.3715-3726
Main Authors: Gansner, John M., Gitlin, Jonathan D.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Animals, Genetically Modified
Base Sequence
birth defects
col10a1
col8a1
Collagen Type VIII - chemistry
Collagen Type VIII - genetics
Collagen Type VIII - metabolism
Conserved Sequence
copper
Embryo, Nonmammalian - embryology
Embryo, Nonmammalian - metabolism
extracellular matrix
Gene Expression Regulation, Developmental
gulliver
lysyl oxidase
Microscopy, Electron, Transmission
Molecular Sequence Data
Mutation - genetics
notochord
Notochord - embryology
Notochord - metabolism
Notochord - ultrastructure
Phenotype
Protein Folding
Protein-Lysine 6-Oxidase - metabolism
Sequence Alignment
zebrafish
Zebrafish - embryology
Zebrafish - genetics
Zebrafish - metabolism
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Summary:Several zebrafish mutants identified in large‐scale forward genetic screens exhibit notochord distortion. We now report the cloning and further characterization of one such mutant, gulliverm208 (gulm208). The notochord defect in gulm208 mutants is exacerbated under conditions of copper depletion or lysyl oxidase cuproenzyme inhibition that are without a notochord effect on wild‐type embryos. The gulm208 phenotype results from a missense mutation in the gene encoding Col8a1, a lysyl oxidase substrate, and morpholino knockdown of col8a1 recapitulates the notochord distortion observed in gulm208 mutants. Of interest, the amino acid mutated in gulm208 Col8a1 is highly conserved, and the equivalent substitution in a closely related human protein, COL10A1, causes Schmid metaphyseal chondrodysplasia. Taken together, the data identify a new protein essential for notochord morphogenesis, extend our understanding of gene–nutrient interactions in early development, and suggest that human mutations in COL8A1 may cause structural birth defects. Developmental Dynamics 237:3715–3726, 2008. © 2008 Wiley‐Liss, Inc.
ISSN:1058-8388
1097-0177
DOI:10.1002/dvdy.21779