title: A nonsense mutation in the 4-hydroxyphenylpyruvic acid dioxygenase gene (Hpd) causes skipping of the constitutive exon and hypertyrosinemia in mouse strain III.
abstract: 4-Hydroxyphenylpyruvic acid dioxygenase (HPD; EC 1.13.11.27) is an important enzyme in tyrosine catabolism in most organisms. Decreased activity of 4-hydroxyphenylpyruvic acid dioxygenase in the liver of mouse strain III is associated with tyrosinemia. We report a nucleotide substitution that generates a termination codon in exon 7 of the 4-hydroxyphenylpyruvic acid dioxygenase gene in III mice. This mutation is associated with partial exon skipping, and most of the mRNA lacks sequences corresponding to exon 7. The partial exon skipping apparently is the result of a nonsense mutation in the exon. Mouse strain III is a model for human tyrosinemia type 3 (McKusick 276710), and this strain together with recently established models for tyrosinemia type 1 will facilitate studies of hereditary tyrosinemias.
authors.affiliation: Department of Pediatrics, Kumamoto University, School of Medicine, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Endo
authors.forename: H
authors.initials: H
authors.lastname: Awata
authors.forename: H
authors.initials: H
authors.lastname: Katoh
authors.forename: I
authors.initials: I
authors.lastname: Matsuda
mesh_terms: D015111:4-Hydroxyphenylpyruvate Dioxygenase / Q000096:biosynthesis / Q000235:genetics*; D000592:Amino Acid Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D018076:DNA, Complementary / Q000302:isolation & purification; D005091:Exons; D015723:Gene Library; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D015183:Restriction Mapping; D014443:Tyrosine / Q000097:blood*
chemical_list: D017931:DNA Primers; D018076:DNA, Complementary; D012333:RNA, Messenger; D014443:Tyrosine; D015111:4-Hydroxyphenylpyruvate Dioxygenase