Abstract
Phenylalanine homeostasis in mammals is primarily controlled by liver phenylalanine hydroxylase (PAH) activity. Inherited PAH deficiency (phenylketonuria or PKU) leads to hyperphenylalaninemia in both mice and humans. A low level of residual liver PAH activity ensures near-normal dietary protein tolerance with normal serum phenylalanine level, but the precise threshold for normal phenylalanine clearance is unknown. We employed hepatocyte transplantation under selective growth conditions to investigate the minimal number of PAH-expressing hepatocytes necessary to prevent hyperphenylalaninemia in mice. Serum phenylalanine levels remained normal in mice exhibiting nearly complete liver repopulation with PAH-deficient hepatocytes (enu2 mice, a model of human PKU, yielded a significant decrease in serum phenylalanine (
Original language | English |
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Pages (from-to) | 337-344 |
Number of pages | 8 |
Journal | Molecular Therapy |
Volume | 12 |
Issue number | 2 |
DOIs | |
Publication status | Published - Aug 2005 |
Keywords
- Hepatocyte transplantation
- Mouse model
- Phenylalanine
- Phenylketonuria
ASJC Scopus subject areas
- Molecular Biology