Determination of the optimal time and dosage of all-trans retinoic acid for induction of murine exencephaly.

Murine exencephaly corresponds to human anencephaly, and provides a model for studying the mechanism of development of the central nervous system. A system which induces exencephaly at an extremely high rate is required in order to examine embryos, before the stage of neural tube closure, as samples of future exencephaly. Herein, we report on a system which is close enough to the best conditions for induction of this malformation, involving ICR mice and all-trans retinoic acid. The intraperitoneal administration of 30 mg/kg of all-trans retinoic acid at 03:00 hr on day 8 (copulatory plug, day 0) induced exencephaly in 81.6% of live embryos, as evaluated on day 10, with a 41.7% embryonic death rate. Earlier administration (more than 3 hr before) greatly increased the rate of embryonic death, whereas later administration resulted in a reduction in the rate of exencephaly. These findings suggest that a specific time during early development is crucial for neural tube closure, and provide a system which may facilitate the study of neural development and the pathophysiology of human anencephaly.