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

doi:10.1016/j.ymthe.2005.03.025

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

IRCCS Ospedale San Raffaele

Research output: Contribution to journal › Article

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
Pages (from-to)	337-344
Number of pages	8
Journal	Molecular Therapy
Volume	12
Issue number	2
DOIs	https://doi.org/10.1016/j.ymthe.2005.03.025
Publication status	Published - Aug 2005

Keywords

Hepatocyte transplantation
Mouse model
Phenylalanine
Phenylketonuria

ASJC Scopus subject areas

Molecular Biology

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Hamman, K., Clark, H., Montini, E., Al-Dhalimy, M., Grompe, M., Finegold, M., & Harding, C. O. (2005). Low therapeutic threshold for hepatocyte replacement in murine phenylketonuria. Molecular Therapy, 12(2), 337-344. https://doi.org/10.1016/j.ymthe.2005.03.025

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AU - Clark, Heather

AU - Montini, Eugenio

AU - Al-Dhalimy, Muhsen

AU - Grompe, Markus

AU - Finegold, Milton

AU - Harding, Cary O.

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