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PMID:7524491
From GONUTS
Gütlich, M, Ziegler, I, Witter, K, Hemmens, B, Hültner, L, McDonald, JD, Werner, T, Rödl, W and Bacher, A (1994) Molecular characterization of HPH-1: a mouse mutant deficient in GTP cyclohydrolase I activity.Biochem. Biophys. Res. Commun. 203:1675-81
| 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-gamma 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. |
| Links | PubMed Online version:10.1006/bbrc.1994.2379 |
Significance
Annotations
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