The fetal alcohol syndrome in mice : an animal model

Although the adverse effects of prenatal exposure to alcohol have been suggested since antiquity, only recently has a 'fetal alcohol syndrome' been described in human beings. Since ethical considerations limit the types of studies possible with humans, an animal model was developed. CBA and C3H female mice, maintained on a liquid Metrecal-ethanol diet, received from 0 to 35 percent ethanol derived calories (EDC) for at least 30 days prior to and throughout gestation. Prenatal death and fetal abnormalities on day 18 of gestation were related to maternal blood alcohol levels which increased with increasing EDC. Reduced fetal weights, skeletal, and neural anomalies were observed at both low and high maternal blood alcohol levels, while cardiac and ocular malformations, similar to those observed in the human syndrome, exhibited both a dose-response effect and strain difference in liability, indicating that maternal chronic alcoholism is embryolethal and teratogenic in mice. In a second experiment, the strain difference in liability was investigated using CBA, C3H, and C57 females maintained on a 20 percent EDC diet and mated in a diallele cross. Prenatal death, malformations, and fetal weights were directly related to maternal blood alcohol levels, indicating a maternal effect. Fetal abnormalities and maternal blood alcohol levels varied with maternal strain (CBA > C3H > C57), and were inversely related to maternal alcohol dehydrogenase activity. Microsomal ethanol oxidizing system induction was directly associated with increased fetal abnormalities, being greatest in CBA females and lowest in C57. The results of this study indicate that malformations observed in the mouse and human syndrome are similar, and that liability for these malformations is dependent on maternal blood alcohol levels, which are determined by the rate of maternal alcohol metabolism as well as the amount of maternal alcohol consumption.Medicine, Faculty ofMedical Genetics, Department ofGraduat