Studies on the genotype-phenotype relation in the hph-1 mouse mutant deficient in guanosine triphosphate (GTP) cyclohydrolase I activity

Toyoki Maeda, Shigehiko Haeno, Kazumi Oda, Daisuke Mori, Hiroshi Ichinose, Toshiharu Nagatsu, Tomokazu Suzuki

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The guanosine triphosphate (GTP) cyclohydrolase I (GTP-CHI) catalyses the rate-limiting step in the de novo synthesis of tetrahydrobiopterin, a cofactor of three aromatic amino acid hydroxylases, one of which is phenylalanine hydroxylase. The hph-1 mouse mutant deficient in GTP-CHI activity exhibits hyperphenylalaninemia which peculiarly disappears at 3 weeks of age, thus corresponding to the increase in liver GTP-CHI activity. The present gas chromatographic-mass spectrometric analysis of the phenylalanine and catecholamine metabolisms demonstrated the former metabolism to remain disturbed even in adult hph-1, which demonstrated a metabolic basis for sensitivity to the phenylalanine challenge in adult hph-1. A Northern blot analysis showed the hepatic GTP-CHI RNA expression in hph-1 at 2, 3 and 4 weeks of age to parallel the peculiar time course of the enzyme activity previously reported. No mutation was detected in either the coding region or the 5' flanking region (nt.-1 to -746) of the GTP-CHI gene of the hph-1. Further molecular genetic analyses are therefore required to elucidate the mechanism of the peculiar phenotype of hph-1. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)50-53
Number of pages4
JournalBrain and Development
Volume22
Issue numberSUPPL. 1
Publication statusPublished - Jan 1 2000

Fingerprint

Guanosine Triphosphate
Genotype
Phenotype
Phenylalanine
Phenylalanine Hydroxylase
Aromatic Amino Acids
Phenylketonurias
5' Flanking Region
Liver
Mixed Function Oxygenases
Northern Blotting
Catecholamines
Molecular Biology
Gases
RNA
Mutation
Enzymes
Genes

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Developmental Neuroscience
  • Clinical Neurology

Cite this

Studies on the genotype-phenotype relation in the hph-1 mouse mutant deficient in guanosine triphosphate (GTP) cyclohydrolase I activity. / Maeda, Toyoki; Haeno, Shigehiko; Oda, Kazumi; Mori, Daisuke; Ichinose, Hiroshi; Nagatsu, Toshiharu; Suzuki, Tomokazu.

In: Brain and Development, Vol. 22, No. SUPPL. 1, 01.01.2000, p. 50-53.

Research output: Contribution to journalArticle

Maeda, T, Haeno, S, Oda, K, Mori, D, Ichinose, H, Nagatsu, T & Suzuki, T 2000, 'Studies on the genotype-phenotype relation in the hph-1 mouse mutant deficient in guanosine triphosphate (GTP) cyclohydrolase I activity', Brain and Development, vol. 22, no. SUPPL. 1, pp. 50-53.
Maeda, Toyoki ; Haeno, Shigehiko ; Oda, Kazumi ; Mori, Daisuke ; Ichinose, Hiroshi ; Nagatsu, Toshiharu ; Suzuki, Tomokazu. / Studies on the genotype-phenotype relation in the hph-1 mouse mutant deficient in guanosine triphosphate (GTP) cyclohydrolase I activity. In: Brain and Development. 2000 ; Vol. 22, No. SUPPL. 1. pp. 50-53.
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