Improved model of maternal phenylketonuria in rats by use of lower dietary concentrations of α-methylphenylalanine and L-phenylalanine in a semipurified diet

Dietary concentrations of 0.5% DL-α-methyl phenylalanine (AMPhe), an inhibitor of phenylalanine hydroxylase, plus 3.0% L-phenylalanine (Phe) have been commonly used in a rat model of maternal phenylketonuria (PKU) . The treatment causes a marked depression of the food consumption and weight gain of the gestating dam. A study was carried out to determine if lowering the dietary concentrations of AMPhe and Phe would improve the condition of the dam, yet permit the maintenance of the high blood Phe concentrations typical of PKU. Long-Evans rats were fed from day 11 until day 20 of gestation on AIN-76A semi-purified diet the same diet containing 0.25%, 0.42%, and 0.50% AMPhe plus L-Phe, using a AMPhe:Phe ratio of 1:6. All dietary levels of AMPhe + Phe except 0.25% AMPhe + 1.5% Phe resulted in similarly elevated fetal brain, fetal plasma or maternal plasma concentrations of Phe. Food intake and maternal weight gain were improved substantially at the lowest dietary levels of AMPhe + Phe. We conclude that the gestational model of PKU using Long- Evans rats fed AIN-76A diet can be improved by reducing the dietary concentrations of AMPhe and Phe to 0.35% and 2.1%, respectively.