Genetic variation in spontaneous and diphenylhydantoin-induced craniofacial malformations in mice.
The mouse strain CL/Fr has been produced by selection for high frequency of cleft lip. It is also sensitive to induction of cleft palate by glucocorticoids, as are its A strain relatives. "Star" strain is free of spontaneous clefts, and is resistant to glucocorticoid teratogenic effects. CL/Fr is also sensitive to toxic effects (80% death at 25 mg/kg) of diphenylhydantoin (DPH), whereas Star is not. Reciprocal crosses between CL/Fr and Star parents were followed for three generations of back-crossing to CL/Fr, with treatment by chronic subcutaneous (SC) DPH injection (20 mg/kg daily from day 0 of pregnancy). Two patterns of response were observed for facial clefts. Primary palate clefts (CL, CLP, lip scars) were not affected by DPH treatment, and showed regression on % CL/Fr genome suggestive of a two- or three-locus recessive effect with the sensitive alleles from CL/Fr. Secondary palate clefts and open eyelids, considered as a group as relatively late developmental defects, showed a pattern suggestive of a dominant gene which increases risk of malformation in DPH-treated embryos, expressed in the crosses, but not in the absence of treatment or in the presence of the full "Star" genome.
D000014:Abnormalities, Drug-Induced / Q000235:genetics*; D000818:Animals; D002972:Cleft Palate / Q000235:genetics; D003433:Crosses, Genetic; D005147:Facial Bones / Q000002:abnormalities* / Q000187:drug effects; D005260:Female; D014644:Genetic Variation; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010672:Phenytoin / Q000633:toxicity*; D012886:Skull / Q000002:abnormalities* / Q000187:drug effects; D013045:Species Specificity
D010672:Phenytoin