The activation of the retinoic acid response element is inhibited in an animal model of congenital diaphragmatic hernia.
Defects very similar to those seen in infants born with congenital diaphragmatic hernias can be induced in rodents by the administration of the teratogen nitrofen. There is an interest in understanding the biochemical mechanisms of nitrofen's actions in hopes of gaining insights into the etiology of congenital diaphragmatic hernia. In this study, we test the hypothesis that nitrofen is acting to perturb the retinoid signaling pathway by utilizing genetically engineered mice that have the lacZ reporter gene linked to a retinoic acid response element (RARE). We demonstrate a pronounced suppression of RARE-lacZ expression by nitrofen in vitro (by approximately 64%) and in vivo (by approximately 43%).
Chen
Miao-hsueh
MH
Division of Human Ecology, University of Texas at Austin, Tex., USA.
MacGowan
Alice
A
Ward
Simon
S
Bavik
Claes
C
Greer
John J
JJ
D000818:Animals; D004195:Disease Models, Animal; D004347:Drug Interactions; D015870:Gene Expression / Q000187:drug effects; D006540:Herbicides / Q000494:pharmacology; D006548:Hernia, Diaphragmatic / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics*; D065630:Hernias, Diaphragmatic, Congenital; D066298:In Vitro Techniques; D007763:Lac Operon; D051379:Mice; D010647:Phenyl Ethers / Q000494:pharmacology; D020218:Response Elements; D013723:Teratogens / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D001616:beta-Galactosidase / Q000378:metabolism
D006540:Herbicides; D010647:Phenyl Ethers; D013723:Teratogens; D014212:Tretinoin; D001616:beta-Galactosidase; C007350:nitrofen