[Experimental teratological studies on facial anomalies induced in mice by bis (dichloroacetyl) diamine. I. Establishment of an animal model of the median cleft face syndrome by the administration of bis (dichloroacetyl) diamine to mice].

Bis (dichloroacetyl) diamine (abbreviated as bisdiamine hereafter) was administered by oral intubation to pregnant Jcl: ICR and A/J mice at a dosage of 3,200 mg/kg/day at days 7.5 and 8.5, 8.5 and 9.5, 9.5 and 10.5 or 10.5 and 11.5 of gestation (VP = day 0). Fetuses were recovered at day 17.5 of gestation following maternal sacrifice. The numbers of resorptions, live fetuses and malformed fetuses were counted in the two strains of mice and the induced craniofacial anomalies were examined macroscopically and histopathologically. In both strains, median facial cleft, cleft palate, exencephalocele and open eyelids were commonly induced craniofacial anomalies. Bisdiamine-induced median facial cleft ranging in severity from minor midfacial disorganization to completely divided nose with a median cleft lip in Jcl: ICR and A/J was strikingly similar to a spectrum of midline defects of the median cleft face syndrome in humans. Histopathological examinations of severe median facial cleft in the two strains revealed that the bifurcated nasal septal cartilage showed irregular hypoplasia and that it was partly disorganized into several nodules of various shapes and sizes. These results indicate that bisdiamine treatment in mice provides a useful animal model of the median cleft face syndrome. Furthermore, higher frequency of median facial cleft and lower mortality in bisdiamine-treated Jcl: ICR indicate that bisdiamine treatment in Jcl: ICR is more effective than that in A/J to make an animal model of this syndrome.