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. 1984 Apr;81(7):2147-51.
doi: 10.1073/pnas.81.7.2147.

Structure, expression, and mutation of the hypoxanthine phosphoribosyltransferase gene

D W Melton, D S Konecki, J Brennand, C T Caskey

Structure, expression, and mutation of the hypoxanthine phosphoribosyltransferase gene

D W Melton et al. Proc Natl Acad Sci U S A. 1984 Apr.

Abstract

The wild-type mouse hypoxanthine phosphoribosyltransferase (HPRT; IMP:pyrophosphate phosphoribosyltransferase, EC 2.4.2.8) gene has been isolated from genomic libraries and its structure has been determined. This X chromosome-linked gene is greater than 33 kilobases long and is split into nine exons. All the exon sequences have been determined, and a single-base substitution in the HPRT cDNA coding sequence from a mouse neuroblastoma cell line that overproduces a mutant HPRT protein has been identified. The 5' end of the gene has been defined, both by nuclease S1 protection and primer extension studies and by a functional assay in which an HPRT minigene, capable of expression in cultured cells, was created by ligating the 5' end of the gene onto wild-type human HPRT cDNA. Sequences normally associated with eukaryotic promoters are not present in the immediate 5'-flanking region of the HPRT gene, which is instead highly G+C rich. This observation is discussed in relation to the possible link between DNA methylation and X-chromosome inactivation.

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