CARDIOVASCULAR DEFECTS AMONG THE PROGENY OF MOUSE PHENYLKETONURIA FEMALES

In a genetic mouse model of human phenylketonuria we have examined the offspring of hyperphenylalaninemic mothers for the presence of cardio vascular defects, an important feature of the pathology of the human m aternal phenylketonuria syndrome. Beginning at 14.5 d after conception (75% through gestation), a variety of cardiovascular defects became a pparent among the progeny of the hyperphenylalaninemic females. These defects ranged from mild to serious and correlated with the maternal b ut not the fetal Pah genotype. Nearly all of the defects were vascular , however, whereas the most reported in humans so far have been cardia c. The predisposing biochemical condition in this mouse disease model seems to be the same as in the human disease; elevated maternal blood phenylalanine levels concentrated across the placental barrier to prod uce a teratogenic developmental environment. This model for congenital cardiovascular defects should enhance two related areas of research. 1) It should allow a more thorough investigation of the relationship b etween maternal diet and maternal phenylketonuria birth defects, and 2 ) it should provide an experimental tool to gain insight into the norm al process of cardiovascular development.