Clinical evidence indicates that prenatal exposure to alcohol may produce a number of morphological and behavioral abnormalities, termed fetal alcohol effects (FAE). Similar findings have been demonstrated in a variety of species, leading to the extensive use of animal models which provide the advantage of precise control over experimental variables. The issue addressed here is that in both humans and nonhumans there is considerable variation in the nature and severity of fetal alcohol effects. That is, one individual may develop highly anomalous characteristics while another shows little effect following equivalent exposure. Several variables have been proposed to account for this variation, including the factor of heredity. Previous work in this laboratory has provided evidence that genetically-mediated sensitivity to alcohol plays an important role in the etiology of FAE; however, no investigations have been carried out regarding the underlying mechanisms. A first step in elucidating these mechanisms is to determine whether they arise from maternal or fetal origin. Locating the source of susceptibility would allow for further investigation as to what specific physiological variables are involved. The proposed studies will employ mice selectively bred for high or low sensitivity to alcohol. Our recent work has shown that offspring of the more sensitive line exhibit overactivity and learning deficits following prenatal alcohol exposure. To separate maternal from fetal variables, we will carry out reciprocal cross breeding and compare the resulting offspring with those of true-bred lineage. Experiments will be performed to assess both morphological and behavioral anomalies. The ultimate goal of these studies is to identify genetically mediated factors which explain variations in symptomology among children born to alcohol-consuming mothers, and thus to aid in the identification of individuals most at risk.
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