Low therapeutic threshold for hepatocyte replacement in murine phenylketonuria

Kelly Hamman, Heather Clark, Eugenio Montini, Muhsen Al-Dhalimy, Markus Grompe, Milton Finegold, Cary O. Harding

Research output: Contribution to journalArticlepeer-review


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 languageEnglish
Pages (from-to)337-344
Number of pages8
JournalMolecular Therapy
Issue number2
Publication statusPublished - Aug 2005


  • Hepatocyte transplantation
  • Mouse model
  • Phenylalanine
  • Phenylketonuria

ASJC Scopus subject areas

  • Molecular Biology


Dive into the research topics of 'Low therapeutic threshold for hepatocyte replacement in murine phenylketonuria'. Together they form a unique fingerprint.

Cite this