Effect of maternal blood phenylalanine level on mouse maternal phenylketonuria offspring

Abstract

The genetic mouse model BTBR-Pah(enu2) was used to more thoroughly investigate the pathogenesis of maternal phenylketonuria (MPKU). More specifically, it was used to examine the effect of maternal blood phenylalanine (PHE) level on the pregnancy outcome of MPKU offspring as determined by certain key measures of development at birth (i.e., head circumference, weight, and crown-rump length of offspring). In this study, we clearly observed that elevated maternal blood PHE levels, whether they were caused by the maternal diet or the maternal genotype, were responsible for fetal abnormalities. As in human MPKU, significant reductions (P < 0.0001) in birth weight, crown-rump length, and head circumference were seen in offspring gestated under the condition of high maternal blood PHE levels. These findings strongly suggest that there are sufficient similarities between human MPKU and MPKU in this mouse model to establish it as a very promising model for future studies designed to characterize human MPKU more thoroughly.