| First Author | Gütlich M | Year | 1994 |
| Journal | Biochem Biophys Res Commun | Volume | 203 |
| Issue | 3 | Pages | 1675-81 |
| PubMed ID | 7524491 | Mgi Jnum | J:20569 |
| Mgi Id | MGI:68654 | Doi | 10.1006/bbrc.1994.2379 |
| Citation | Gutlich M, et al. (1994) Molecular characterization of HPH-1: a mouse mutant deficient in GTP cyclohydrolase I activity. Biochem Biophys Res Commun 203(3):1675-81 |
| abstractText | 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. |
