Prolyl 4-hydroxylase is required for viability and morphogenesis in Caenorhabditis elegans
Prolyl 4-hydroxylase is required for viability and morphogenesis in Caenorhabditis elegans
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DOI：
10.1073/pnas.97.9.4736
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发表时间：
2000-04-25
影响因子：
11.1
通讯作者：
Kimble, J
中科院分区：
文献类型：
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作者：
Friedman, L;Higgin, JJ;Kimble, J
秀丽隐杆线虫的基因组具有两个基因，dpy-18和phy-2，它们编码脯氨酰4-羟化酶的α亚基。我们在每个基因内产生缺失以消除动物的脯氨酰4-羟化酶活性。dpy-18突变体具有异常的身体形态，与脯氨酰4-羟化酶在身体角质层形成中的作用一致。phy-2突变体在表型上是野生型。然而，DPY-18; PHY-2双突变体不能存活，这表明脯氨酰4-羟化酶的重要作用通常由DPY-18或PHY-2完成。通过脯氨酰4-羟化酶的小分子抑制剂模拟了双突变的影响，验证了遗传结果，并表明C。线虫可以作为发现新抑制剂的模型系统。
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.