Characterization of the mouse phenylalanine hydroxylase mutation Pah(enu3)

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dc.contributor.author Haefele, Mark J. en_US
dc.contributor.author White, Gabriele en_US
dc.contributor.author McDonald, J. David en_US
dc.date.accessioned 2012-01-24T17:48:39Z
dc.date.available 2012-01-24T17:48:39Z
dc.date.issued 2001-01 en_US
dc.identifier 11161825 en_US
dc.identifier 9805456 en_US
dc.identifier S1096-7192(00)93104-4 en_US
dc.identifier.citation Molecular genetics and metabolism. 2001 Jan; 72(1): 27-30. en_US
dc.identifier.issn 1096-7192 en_US
dc.identifier.uri http://dx.doi.org/10.1006/mgme.2000.3104
dc.identifier.uri http://hdl.handle.net/10057/4141
dc.description Click on the DOI link below to access the article (may not be free). en_US
dc.description.abstract Phenylketonuria (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.iso eng en_US
dc.publisher Academic Press en_US
dc.relation.ispartofseries Molecular genetics and metabolism en_US
dc.source NLM en_US
dc.subject Research Support, U.S. Gov't, Non-P.H.S. en_US
dc.subject.mesh Alleles en_US
dc.subject.mesh Animals en_US
dc.subject.mesh Base Sequence en_US
dc.subject.mesh DNA Mutational Analysis en_US
dc.subject.mesh DNA, Complementary/metabolism en_US
dc.subject.mesh Disease Models, Animal en_US
dc.subject.mesh Exons en_US
dc.subject.mesh Frameshift Mutation en_US
dc.subject.mesh Gene Deletion en_US
dc.subject.mesh Humans en_US
dc.subject.mesh Introns en_US
dc.subject.mesh Male en_US
dc.subject.mesh Mice en_US
dc.subject.mesh Models, Genetic en_US
dc.subject.mesh Molecular Sequence Data en_US
dc.subject.mesh Mutagenesis en_US
dc.subject.mesh Mutation en_US
dc.subject.mesh Mutation, Missense en_US
dc.subject.mesh Phenylalanine/biosynthesis en_US
dc.subject.mesh Phenylalanine Hydroxylase/genetics en_US
dc.subject.mesh Phenylketonurias/genetics en_US
dc.subject.mesh RNA Splice Sites en_US
dc.subject.mesh RNA, Messenger/metabolism en_US
dc.subject.mesh Sequence Homology, Nucleic Acid en_US
dc.title Characterization of the mouse phenylalanine hydroxylase mutation Pah(enu3) en_US
dc.type Article en_US
dc.description.version peer reviewed en_US
dc.rights.holder Copyright 2001 Academic Press. en_US

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