Characterization, evolutionary relationships, and chromosome location of processed mouse HPRT pseudogene

Abstract

Studies on a cell line with amplified copies of the mouse hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene and HPRT gene transfer experiments revealed the existence of a nonfunctional HPRT-related sequence in the mouse genome. This sequence was isolated and found to be a processed HPRT pseudogene. With the exception of a small internal deletion, the pseudogene is believed to comprise a complete reverse transcript of HPRT mRNA, although the 3' end of the pseudogene was lost in the cloning process. A probe from a region flanking the mouse pseudogene was used to investigate the evolutionary relationships of mammalian HPRT pseudogenes. The pseudogenes in mouse and Chinese hamster appear to have a common origin, but no homology to any of the four known human HPRT pseudogenes was detected. A pseudogene-linked restriction fragment length polymorphism was used to map the pseudogene to the distal end of mouse chromosome 17.

Quantitative Trait Loci Affecting Methamphetamine Responses in BXD Recombinant Inbred Mouse Strains

“…The Hprt-ps1 marker locus on chromosome 17, for instance, was associated with psychostimulant response in all of these studies. This is a pseudogene for the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) and, therefore, does not appear to translate any functional proteins (Isamat et al, 1988). It is interesting, however, that an HPRT enzyme deficiency is associated with the motor disorder Lesch-Nyhan syndrome in humans and with alterations in dopaminergic activity in motor nuclei and increased sensitivity to amphetamine-induced locomotion and stereotypy in mice (Jinnah et al, 1991(Jinnah et al, , 1994), suggesting the possibility that polymorphisms in the retroposed HPRT pseudogene may differentially regulate (as endogenous antisense nucleotides) the HPRT gene itself (see, for example, Zhou et al, 1992;Akagi et al, 1994;Carlton et al, 1994;Manjanatha et al, 1994;Kas et al, 1995;Leedman et al, 1995).…”