Cranio-facial dysmorphism: experimental study in the mouse, clinical applications

To obtain a better understanding of mandibulo-facial dysostosis and hemicra niofacial microsomia in man, the authors carried out a histologic and scann ing electron microscope study of the facial malformations produced in mouse embryos by retinoic acid and methyl-triazene. The administration of 400 mg /kg 13 cis-retinoic acid (RA) to pregnant C57BL mice on day 9 of gestation produced anomalies of the cephalic extremity in the embryos resembling huma n mandibulo-facial dysostosis. The 64 embryos collected presented hypoplasi a of the branchial arches or the snout in 79% of cases, auricular anomalies in 47% and ophthalmic anomalies in 12.5%. Fourteen NMRI mice on day 10.5 o f gestation were treated with 1.5 mg (0.5 mg/kg) methyl-triazene (Methyl). The 126 embryos collected had developed a very high percentage of micromand ibles and anomalies of both embryonic ears (94.6% to 100%). Finally, althou gh the facial anomalies produced by retinoic acid resemble the human mandib ulo-facial dysostosis syndrome, no correlation was found between hemicranio facial microsomia and the administration of methyltriazene.