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 gene
rated deletions within each gene to eliminate prolyl 4-hydroxylase activity
from the animal. The dpy-18 mutant has an aberrant body morphology, consis
tent 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 do
uble mutant is not viable, suggesting an essential role for prolyl 4-hydrox
ylase 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. elega
ns can serve as a model system for the discovery of new inhibitors.