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 f or studying the mechanism of development of the central nervous system. A s ystem which induces exencephaly at an extremely high rate is required in or der 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 m ice and all-trans retinoic acid. The intraperitoneal administration of 30 m g/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, wi th a 41.7% embryonic death rate. Earlier administration (more than 3 hr bef ore) greatly increased the rate of embryonic death, whereas later administr ation resulted in a reduction in the rate of exencephaly. These findings su ggest that a specific time during early development is crucial for neural t ube closure, and provide a system which may facilitate the study of neural development and the pathophysiology of human anencephaly. (C) 1999 Wiley-Li ss, Inc.