Abstract
The human fetal hydantoin syndrome includes cleft (lip) palate. Phenytoin also produces cleft (lip) palate in A/J mice which is sensitive to cortisone-induced cleft palate. Recently, we have shown that the strain differences in susceptibility to cortisone-induced cleft palate in mice can be explained in terms of variation in levels of fetal palatal glucocorticoid receptors, which in turn are regulated by H-2 linked gene(s). Thus, we have tested the hypothesis that phenytoin may have similar genetic differences in susceptibility to the production of this defect in mice as does cortisone. Phenytoin was administered at 50 mgs/kg from the 11-14 days of gestation in the strains A/J (H-2a), B10 (H-2b), and B10.A (having H-2a but otherwise 99.5% of genetic background of B10). Susceptibility to phenytoin-induced cleft palate is high in A/J (43.8% of offspring) and B10.A (32.9%) but low in B10 (1.6%). Therefore, a gene controlling phenytoin-induced cleft palate is also located in or near the H-2 locus. These results give the first evidence of a genetic control mechanism (by a gene in or near the H-2 locus) for susceptibility to a congenital malformation (cleft palate) to a xenobiotic (phenytoin).
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Goldman, A., Katsumata, M. & Gasser, D. 913 FETAL HYDANTOIN SYNDROME: SUSCEPTIBILITY TO PHENYTOIN-INDUCED CLEFT (LIP) AND PALATE LINKED TO H-2 LOCUS IN MICE. Pediatr Res 12 (Suppl 4), 516 (1978). https://doi.org/10.1203/00006450-197804001-00918
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DOI: https://doi.org/10.1203/00006450-197804001-00918