title: Expression of human HPRT in the central nervous system of transgenic mice.
abstract: Severe deficiency of hypoxanthine phosphoribosyltransferase (HPRT) in man results in the Lesch-Nyhan syndrome, an X-linked neurological disorder characterized by mental retardation, choreoathetosis and a compulsive tendency towards self-mutilation. Although the HPRT gene is normally constitutively expressed in all tissues at low levels, expression is elevated approximately fourfold in several regions of the central nervous system, particularly in the basal ganglia. The relationships between HPRT deficiency, tissue-specific alterations of nucleotide metabolism and the neuropathology of the Lesch-Nyhan syndrome remain unclear. Here we have microinjected recombinant molecules containing human HPRT (hHPRT) complementary DNA, the mouse metallothionein-I (MT-I) promoter and the 3'-untranslated portion of the human growth hormone (hGH) gene into mouse embryos to produce transgenic animals that express hHPRT on induction by cadmium. The hHPRT cDNA in these experiments contained 88 base pairs (bp) of 5'-untranslated and 190 bp of 3'-untranslated sequences, and the full-length coding sequence. We studied the in vivo expression of this MT-hHPRT fusion gene and observed preferential hHPRT expression in tissues of the central nervous system (CNS). This study suggests that sequences within the hHPRT transcript (cDNA) influence CNS expression via increased synthesis or stability of messenger RNA.
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology; D002104:Cadmium / Q000494:pharmacology; D004262:DNA Restriction Enzymes; D005260:Female; D005796:Genes / Q000187:drug effects; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D051379:Mice; D009206:Myocardium / Q000201:enzymology; D009928:Organ Specificity; D010957:Plasmids; D011555:Pseudopregnancy; D013045:Species Specificity; D013154:Spleen / Q000201:enzymology
chemical_list: D002104:Cadmium; D007041:Hypoxanthine Phosphoribosyltransferase; D004262:DNA Restriction Enzymes