Experimental teratological studies with the mouse CNS mutations cranioschisis and delayed splotch.

Teratological experiments were made with a recessive mouse gene (cranioschisis) causing exencephaly and a semidominant gene (delayed splotch) causing spina bifida. In studies with the cranioschisis gene administration of warfarin and thyroxine resulted in frequencies of exencephaly significantly below that expected of a recessive trait, perhaps indicating selective elimination of abnormal conceptuses. Studies with the delayed splotch gene tested the hypothesis that offspring with a hereditary defect of neural-tube closure have other, unexpressed CNS defects, which may be elicited by teratological impulses. This proposition was decisively upheld by administering 5-bromo-2'-deoxyuridine, cadmium sulfate and retinoic acid, as these treatments all caused significantly greater frequencies of induced exencephaly in offspring with spina bifida than in their genetically normal littermates.