Investigation on the role of genetic predisposing factors in developing fetal toxicity of ethanol is continued. Involvement of genetic factors in the pathogenesis of fetal alcohol syndrome (FAS) is strongly implicated from the facts that (a) only 33% of alcoholic mothers give birth to FAS babies, and (b) there are instances of fraternal twins born of chronic alcoholic mothers where only one of the twins is afflicted with FAS. During the past year, we have shown that precipitating thiamine deficiency in the mother can lead to intrauterine growth retarded (IUGR) babies in the rat. These IUGR babies have been followed-up for their postnatal growth and for their learning ability. We found that the IUGR babies born of thiamine deficient mothers remained significantly lower in their body weight and size, and they were significantly deficient in their learning ability as judged from their exploratory behavior studies compared to their control counterparts. These data suggest that postnatal growth retardation and deficient learning ability, characteristic features of FAS, may be related to thiamine deficiency in utero. Since there are some strains of rats which are more susceptible to see if they have a transketolase with a high Km for thiamine pyrophosphate (TPP). If so, these animals will be used as models to study predisposing genetic factors in FAS in more detail. To characterize these animals biochemically, we have developed a method for purifying the apotransketolase from various tissues to determine the Km for TPP. Since the effects of thiamine deficiency is most pronounced in the brain and since most of the studies on transketolase are done on skin fibroblasts or RBC's, it will be important to show whether or not the Km for TPP of the fibroblast or RBC enzyme is similar to that of the brain enzyme. The new purification technique is now being used to delineate this.
