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Prolyl 4-hydroxylase is required for viability and morphogenesis in Caenorhabditis elegans.


ABSTRACT: The genome of Caenorhabditis elegans possesses two genes, dpy-18 and phy-2, that encode alpha subunits of the enzyme prolyl 4-hydroxylase. We have generated deletions within each gene to eliminate prolyl 4-hydroxylase activity from the animal. The dpy-18 mutant has an aberrant body morphology, consistent with a role of prolyl 4-hydroxylase in formation of the body cuticle. The phy-2 mutant is phenotypically wild type. However, the dpy-18; phy-2 double mutant is not viable, suggesting an essential role for prolyl 4-hydroxylase that is normally accomplished by either dpy-18 or phy-2. The effects of the double mutation were mimicked by small-molecule inhibitors of prolyl 4-hydroxylase, validating the genetic results and suggesting that C. elegans can serve as a model system for the discovery of new inhibitors.

SUBMITTER: Friedman L 

PROVIDER: S-EPMC18302 | biostudies-literature | 2000 Apr

REPOSITORIES: biostudies-literature

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Prolyl 4-hydroxylase is required for viability and morphogenesis in Caenorhabditis elegans.

Friedman L L   Higgin J J JJ   Moulder G G   Barstead R R   Raines R T RT   Kimble J J  

Proceedings of the National Academy of Sciences of the United States of America 20000401 9


The genome of Caenorhabditis elegans possesses two genes, dpy-18 and phy-2, that encode alpha subunits of the enzyme prolyl 4-hydroxylase. We have generated deletions within each gene to eliminate prolyl 4-hydroxylase activity from the animal. The dpy-18 mutant has an aberrant body morphology, consistent with a role of prolyl 4-hydroxylase in formation of the body cuticle. The phy-2 mutant is phenotypically wild type. However, the dpy-18; phy-2 double mutant is not viable, suggesting an essentia  ...[more]

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