title: Characterization of mutations at the mouse phenylalanine hydroxylase locus.
abstract: Two genetic mouse models for human phenylketonuria have been characterized by DNA sequence analysis. For each, a distinct mutation was identified within the protein coding sequence of the phenylalanine hydroxylase gene. This establishes that the mutated locus is the same as that causing human phenylketonuria and allows a comparison between these mouse phenylketonuria models and the human disease. A genotype/phenotype relationship that is strikingly similar to the human disease emerges, underscoring the similarity of phenylketonuria in mouse and man. In PAHENU1, the phenotype is mild. The Pahenu1 mutation predicts a conservative valine to alanine amino acid substitution and is located in exon 3, a gene region where serious mutations are rare in humans. In PAHENU2, the phenotype is severe. The Pahenu2 mutation predicts a radical phenylalanine to serine substitution and is located in exon 7, a gene region where serious mutations are common in humans. In PAHENU2, the sequence information was used to devise a direct genotyping system based on the creation of a new Alw26I restriction endonuclease site.
authors.affiliation: Department of Biological Sciences, Wichita State University, Kansas 67260, USA. mcdonald@wsuhub.uc.twsu.edu
authors.forename: J D
authors.initials: JD
authors.lastname: McDonald
authors.forename: C K
authors.initials: CK
authors.lastname: Charlton
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D009154:Mutation; D010651:Phenylalanine Hydroxylase / Q000235:genetics*; D010661:Phenylketonurias / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D010651:Phenylalanine Hydroxylase