Molecular characterization of HPH-1: a mouse mutant deficient in GTP cyclohydrolase I activity

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Authors
Gutlich, M.
Ziegler, I.
Witter, K.
Hemmens, B.
Hultner, L.
McDonald, J. David
Werner, T.
Rodl, W.
Bacher, A.
Issue Date
1994-09
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Article
Language
en_US
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Abstract

GTP cyclohydrolase I catalyzes the initial and rate limiting step of the biosynthesis of tetrahydrobiopterin, the cofactor for aromatic amino acid hydroxylation. The mouse mutant HPH-1, previously generated by chemical mutagenesis, shows a phenylketonuria due to decreased hepatic GTP cyclohydrolase I activity. We show that both parameters GTP cyclohydrolase I activity and tetrahydrobiopterin synthesis significantly increase after weaning, but remain reduced during the lifetime. In the wild type mouse (C57BL/6), interferon-γ and kit ligand induce GTP cyclohydrolase I activity in primed T-cells and in bone marrow-derived mast cells, respectively. The same is true for the HPH-1 mutant, but the absolute values remain lower throughout. The open reading frame of GTP cyclohydrolase I is not affected by the hph-1 mutation as shown by sequencing. Northern blot analysis demonstrates a marked decrease in the steady state mRNA level specific for GTP cyclohydrolase I.

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Gutlich, M.; Ziegler, I.; Witter, K.; Hemmens, B.; Hultner, L.; Mcdonald, J. David; Werner, T.; Rodl, W.; Bacher, A. 1994. Molecular Characterization of HPH-1: A Mouse Mutant Deficient in GTP Cyclohydrolase I Activity. Biochemical and Biophysical Research Communications, v.203 no. 3 pp.1675-1681
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Elsevier
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0006-291X
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