Prolyl 4-hydroxylase is required for viability and morphogenesis in Caenorhabditis elegans.
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.
Friedman
L
L
Departments of Biochemistry and Chemistry, and Howard Hughes Medical Institute, University of Wisconsin, Madison, WI 53706, USA.
Higgin
J J
JJ
Moulder
G
G
Barstead
R
R
Raines
R T
RT
Kimble
J
J
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000235:genetics* / Q000502:physiology; D002645:Chickens; D008040:Genetic Linkage; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D009024:Morphogenesis; D016296:Mutagenesis; D010802:Phylogeny; D011393:Procollagen-Proline Dioxygenase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D015203:Reproducibility of Results; D016415:Sequence Alignment; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid
D046911:Macromolecular Substances; D011393:Procollagen-Proline Dioxygenase