A Study on Production of a New Model of Cleft Lip and Cleft Palate by Fetal Manipulation

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We carried out experiments on the production of an animal model for clarification of the developmental factors of craniofacial malformations including cleft lip and palate and the mode of progression of facial deformations associated with malformations during the fetal period.1. Exo utero surgery was performed in mouse fetuses. At a fetal age of 10-12 days when the basic morphology of the fetal face is completed, the face primodium was injured by electrocoagulation using fine glass needle electrodes or argon laser photocoagulation, inducing facial deformations during subsequent growth. By these procedures, we searched for a fetal manipulation method to clarify the mode of facial growth from the formation of the mouse embryonic facial projection to birth.2. Exo utero fetuses in which the face was directly invaded via the decidua, yolk sac, and the aminon at the age of 11-12 days subsequently showed growth similar to that in the surrounding intrauterine fetuses.3. Of exo utero fetuses in which the face was invaded by electrocoagulation using fine glass needle electrodes, about 50% survived to a fetal age of 12 days and showed asymmetrical face and secondary palatal tissue defects in the deep area.4. Of exo utero fetuses in which the face was invaded by argon laser photocoagulation on 11 days of gestation, 20% survived to the term and primarily showed asymmetrical facial morphology due to tissue difects in the facial surface layr.5. The malformation characterized by maxillary asymmetrical growth that occurred in a CL/Fr mouse colony was established as a genetic substrain.These results suggest that congenital craniofacial deformations can be induced by fetal face manipulation. This study may provide useful data for the establishment of experimental systems.