Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.8 (hypoxanthine-guanine phosphoribosyltransferase)
 2,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have used a highly sensitive biochemical microassay to monitor the expression of a cloned minigene for hypoxanthine phosphoribosyl transferase (HPRT, EC.2.4.2.8) in preimplantation mouse embryos. The mouse HPRT promoter and the mouse metallothionein promoter (MT-I) function equally well in embryos at the 2-cell stage whereas the viral SV40 promoter does not allow HPRT expression. Induced HPRT activity from the MT-I HPRT minigene construct occurs in cleavage embryos cultured in the presence of cadmium. In contrast, negation of enzyme expression from the injected minigene DNA is mediated by simultaneous injection of HPRT antisense DNA.
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PMID:Expression of injected HPRT minigene DNA in mouse embryos and its inhibition by antisense DNA. 247 90

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.
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PMID:Expression of human HPRT in the central nervous system of transgenic mice. 299 15

Cell lines were established which produced high titers (approximately 10(6) infectious units per ml) of amphotropic, replication-defective recombinant retroviruses which transduced sequences encoding either human purine nucleoside phosphorylase (PNP) or adenosine deaminase (ADA). These viruses also contained a human hypoxanthine phosphoribosyltransferase gene as a selectable marker and a mouse metallothionein promoter (MMP) sequence just upstream from the PNP or ADA genes. Virus structure was maintained through the replication cycle if a short (216-base pair) MMP sequence was used. However, the use of a longer (1,834-base pair) MMP sequence resulted in the deletion of a significant portion of the recombinant virus genome, including the transcriptional regulatory elements of the MMP sequence. Northern analysis indicated a predominance of genome length transcripts in cells infected with deleted virus. The demonstration of substantial human PNP or ADA activity in virus-infected mouse fibroblasts by isozyme analysis suggested that active gene product was translated from either spliced or bicistronic message. The deleted ADA and PNP viruses were introduced into mouse hematopoietic stem cells by cocultivating freshly explanted bone marrow with virus producer cells. The infected marrow cells were injected into irradiated, syngeneic recipient mice, and the presence of integrated ADA or PNP proviral sequences was demonstrated in the DNA of spleen colonies by Southern analysis. Failure of these integrated proviral sequences to express active, human isozyme in spleen colony tissue indicated the existence of some regulatory constraint not active in cultured mouse cells.
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PMID:Human purine nucleoside phosphorylase and adenosine deaminase: gene transfer into cultured cells and murine hematopoietic stem cells by using recombinant amphotropic retroviruses. 310 47

Recombinant vectors containing the mouse metallothionein-I gene (MT-I) and the Escherichia coli xanthine-guanine phosphoribosyltransferase gene (gpt) were used to transfect human hgprt- HeLa cells. Transfected MT-I genes are transcriptionally regulated by cadmium but not by glucocorticoids. S1 mapping indicates that the transcripts from transfected MT-I genes begin at the correct transcription initiation site. We also transfected mouse tk- L cells with a vector containing the mouse MT- I gene and the herpes simplex virus-I thymidine kinase gene. MT-I gene transcription is regulated by cadmium but not by glucocorticoids in this homologous system as well. Finally, we fused the MT-I gene promoter/regulatory region to the thymidine kinase structural gene. Thymidine kinase activity is regulated by cadmium when this fusion gene is transfected into mouse tk- L cells. Deletion mapping experiments indicate that the DNA sequences necessary for regulation of the MT-I gene by cadmium lie within 148 bp of its transcription start site.
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PMID:The mouse metallothionein-I gene is transcriptionally regulated by cadmium following transfection into human or mouse cells. 695 27

The toxicity and mutagenicity (including the mutation spectrum induced) of dacarbazine, a methylating cytostatic drug, was examined in CHO cells expressing different levels of the repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT). Expression of low or high levels of a transfected human MGMT gene under the control of the metallothionein promoter protected the cells against dacarbazine-induced toxicity and mutagenesis. In the absence of MGMT expression, the mutation spectrum in the HPRT locus was dominated by GC-->AT transitions (mostly found at 5'Pu-G sequences), while there were also a few AT-->GC transitions. Expression MGMT was associated with a substantial decrease of GC-->AT mutations, suggesting that these mutations arose primarily via O(6)-methylguanine. These data illustrate the important role of the latter lesion in the drug's mutagenic and cytotoxic activity.
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PMID:Toxicity, mutation frequency and mutation spectrum induced by dacarbazine in CHO cells expressing different levels of O(6)-methylguanine-DNA methyltransferase. 1075 9