Characterizing Developmental Defects in an Avian Model of Maternal PKU

Abstract

Maternal phenylketonuria [MPKU] is a syndrome of multiple congenital anomalies including cardiovascular malformations [CVMs], brain and growth restriction when a mother with Phenylketonuria [PKU] does not control her dietary intake of Phenylalanine [Phe]. In this study, we aim to establish and characterize an avian model of MPKU. We focused on early developmental defects. METHODS: We investigated the effect of 2500?M Phe exposure by inovo yolk injection. Following the injection, the embryos underwent further development for 48 hours until dissection was performed. At HH14-17, India ink was injected into the yolk as a contrast dye. Images were taken of embryos and they were scored based on Drake et. al (2006.) RESULTS: Embryos exposed to high Phe displayed gross morphological changes including developmental and growth delays, anterior and posterior abnormalities, and torsion defects. FUTURE STUDIES: Histological analysis is underway to determine changes in heart development. Currently there is no data interrogating the mechanism by which Phe causes heart defects. We plan to utilize this model to define the mechanism of Phe cardiac teratogenicity which is critical for improving MPKU treatments and outcomes.