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dc.contributor.authorHaefele, Mark J.en_US
dc.contributor.authorWhite, Gabrieleen_US
dc.contributor.authorMcDonald, J. Daviden_US
dc.date.accessioned2012-01-24T17:48:39Z
dc.date.available2012-01-24T17:48:39Z
dc.date.issued2001-01en_US
dc.identifier11161825en_US
dc.identifier9805456en_US
dc.identifierS1096-7192(00)93104-4en_US
dc.identifier.citationMolecular genetics and metabolism. 2001 Jan; 72(1): 27-30.en_US
dc.identifier.issn1096-7192en_US
dc.identifier.urihttp://dx.doi.org/10.1006/mgme.2000.3104
dc.identifier.urihttp://hdl.handle.net/10057/4141
dc.descriptionClick on the DOI link below to access the article (may not be free).en_US
dc.description.abstractPhenylketonuria (PKU) is an inborn error of metabolism that is inherited in an autosomal recessive manner. It arises from a deficiency of phenylalanine hydroxylase, which is responsible for converting phenylalanine to tyrosine and thereby hastening its catabolism. To produce mouse models for the study of PKU, male mice were mutagenized with ethylnitrosourea and their progeny were screened for the elevated phenylalanine levels characteristic of phenylalanine hydroxylase deficiency. Of three mutant alleles recovered, two (Pah(enu1) and Pah(enu2)) were characterized previously and shown to be missense mutations. Sequencing of phenylalanine hydroxylase cDNA from the third mutant allele, Pah(enu3), revealed that two differently sized transcripts were being produced. These transcripts contained either a 5-nucleotide insertion or a 5-nucleotide deletion and both of these modifications occurred at the same location, the exon 11-exon 12 junction. Sequencing of the exon 11-intron 11 boundary revealed a T --> G transversion in the invariant GT dinucleotide of the wild-type 5' splice donor site. The analogous human Pah mutation would be called c.1199 + 2T > G. Sequence analysis also revealed two cryptic splice donor sites, upstream and downstream of the wild-type splice site, that appear to be used when the wild type is ablated and to thereby yield the observed differently sized transcripts. The 5-nucleotide insertion and the 5-nucleotide deletion are both predicted to cause frame shifting in exon 12 and exon 13, leading to premature termination.en_US
dc.language.isoengen_US
dc.publisherAcademic Pressen_US
dc.relation.ispartofseriesMolecular genetics and metabolismen_US
dc.sourceNLMen_US
dc.subjectResearch Support, U.S. Gov't, Non-P.H.S.en_US
dc.subject.meshAllelesen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBase Sequenceen_US
dc.subject.meshDNA Mutational Analysisen_US
dc.subject.meshDNA, Complementary/metabolismen_US
dc.subject.meshDisease Models, Animalen_US
dc.subject.meshExonsen_US
dc.subject.meshFrameshift Mutationen_US
dc.subject.meshGene Deletionen_US
dc.subject.meshHumansen_US
dc.subject.meshIntronsen_US
dc.subject.meshMaleen_US
dc.subject.meshMiceen_US
dc.subject.meshModels, Geneticen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshMutagenesisen_US
dc.subject.meshMutationen_US
dc.subject.meshMutation, Missenseen_US
dc.subject.meshPhenylalanine/biosynthesisen_US
dc.subject.meshPhenylalanine Hydroxylase/geneticsen_US
dc.subject.meshPhenylketonurias/geneticsen_US
dc.subject.meshRNA Splice Sitesen_US
dc.subject.meshRNA, Messenger/metabolismen_US
dc.subject.meshSequence Homology, Nucleic Aciden_US
dc.titleCharacterization of the mouse phenylalanine hydroxylase mutation Pah(enu3)en_US
dc.typeArticleen_US
dc.description.versionpeer revieweden_US
dc.rights.holderCopyright 2001 Academic Press.en_US


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