Postnatal growth in a mouse genetic model of classical phenylketonuria

Because of the ethical problems of withholding dietary treatment from patients with phenylketonuria, effectively studying long-term effects such as postnatal growth rates is difficult or impossible. The only literature available on the growth rate of phenylketonurics dates from the era before effective dietary treatment regimens were instituted routinely. Although some of these studies suggest that these patients have a reduced growth rate, whether this is a consistent feature of the untreated phenylketonuric is unclear. The mutant mouse line BTBR-Pahenu, a genetic model for human phenylketonuria, provides an opportunity to conduct studies that will clarify this issue. In this study, the weights of newborn mice were monitored from about 7 to 40 days after birth. Comparison to heterozygous, sex-matched littermates revealed a reduction in the size of homozygous mutants throughout the study. Therefore, reduced postnatal growth is an abiding feature of phenylketonuria in this mouse model. This finding not only helps to document the association between size reduction and untreated phenylketonuria but also sets the stage for studies designed to investigate the means by which size reduction occurs.