Retinoic acid, cortisone, or thyroxine suppresses the mutant phenotype of the eyelid development mutation, lgMl, in mice.
The development of the mammalian eyelid is one of the last major morphogenetic events during prenatal development. The eyelids originate as outgrowths of epithelium and mesenchyme above and below the eye; they grow and flatten across the eyes, and meet and fuse firmly but temporarily until several days after birth in mice. In mouse lidgap mutants, eyelid development fails. Previously, we have shown that normal eyelid development can be induced in lidgap mutants by maternal treatment with cortisone or thyroxine. These hormones have been reported to interact with members of a receptor superfamily, and their response elements have been shown to induce transcription of hormone-regulated genes; retinoic acid also interacts with members of this superfamily. The purposes of our study were to examine the joint effect of thyroxine and cortisone on induced eyelid development in lidgap-Miller mutant fetuses (lgMl/lgMl), to test for synergism, and also to test whether retinoic acid also induces eyelid development in this mutant. We found that the combined effect of thyroxine and cortisone was significantly greater than that of either hormone alone, but that the dose-response slopes (log dose, probit scale) for eyelid development induced by cortisone alone or by cortisone preceded by 0.1 mg thyroxine were parallel, suggesting that their action is additive, not synergistic. We found that retinoic acid administered on day 14 of gestation induced eyelid development in lgMl/lgMl mutant fetuses, with a significant dose response and ED50 of 24 +/- 6 mg/kg. The response was treatment-time dependent, with optimal responses after day 14 or 11 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Juriloff
D M
DM
Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
Harris
M J
MJ
D000818:Animals; D003348:Cortisone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005143:Eyelids / Q000187:drug effects* / Q000196:embryology*; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009154:Mutation; D010641:Phenotype; D013974:Thyroxine / Q000494:pharmacology*; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology*
D014212:Tretinoin; D013974:Thyroxine; D003348:Cortisone