hypoxanthine phosphoribosyltransferase

Summary

Summary: An enzyme that catalyzes the conversion of 5-phosphoribosyl-1-pyrophosphate and hypoxanthine, guanine, or 6-mercaptopurine to the corresponding 5'-mononucleotides and pyrophosphate. The enzyme is important in purine biosynthesis as well as central nervous system functions. Complete lack of enzyme activity is associated with the LESCH-NYHAN SYNDROME, while partial deficiency results in overproduction of uric acid. EC 2.4.2.8.

Top Publications

  1. ncbi HPRT-deficient (Lesch-Nyhan) mouse embryos derived from germline colonization by cultured cells
    M Hooper
    Nature 326:292-5. 1987
  2. pmc Purinergic signaling in human pluripotent stem cells is regulated by the housekeeping gene encoding hypoxanthine guanine phosphoribosyltransferase
    Lina Mastrangelo
    Department of Pediatrics, Center for Neural Circuits and Behavior, University of California at San Diego School of Medicine, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 109:3377-82. 2012
  3. pmc MicroRNA-mediated dysregulation of neural developmental genes in HPRT deficiency: clues for Lesch-Nyhan disease?
    Ghiabe Henri Guibinga
    Department of Pediatrics, Center for Neural Circuits and Behavior and Rady Children s Hospital, School of Medicine, University of California San Diego, San Diego, CA 92093 0634, USA
    Hum Mol Genet 21:609-22. 2012
  4. pmc Mechanism of radiation-induced bystander effect: role of the cyclooxygenase-2 signaling pathway
    Hongning Zhou
    Center for Radiological Research, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 102:14641-6. 2005
  5. pmc Deficiency of the housekeeping gene hypoxanthine-guanine phosphoribosyltransferase (HPRT) dysregulates neurogenesis
    Ghiabe Henri Guibinga
    Department of Pediatrics, Center for Molecular Genetics, University of California, San Diego School of Medicine, La Jolla, California 92093 0634, USA
    Mol Ther 18:54-62. 2010
  6. pmc Hypoxanthine-guanine phosphoribosyl transferase regulates early developmental programming of dopamine neurons: implications for Lesch-Nyhan disease pathogenesis
    Irene Ceballos-Picot
    School of Medicine, Paris Descartes University, 75006 Paris, France
    Hum Mol Genet 18:2317-27. 2009
  7. ncbi HPRT mutants induced in bystander cells by very low fluences of alpha particles result primarily from point mutations
    L Huo
    Department of Cancer Cell Biology, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA
    Radiat Res 156:521-5. 2001
  8. pmc HPRT deficiency coordinately dysregulates canonical Wnt and presenilin-1 signaling: a neuro-developmental regulatory role for a housekeeping gene?
    Tae Hyuk Kang
    Department of Pediatrics, Center for Neural Circuit and Behavior and San Diego Rady Children s Hospital, University of California San Diego, San Diego School of Medicine, La Jolla, California, United States of America
    PLoS ONE 6:e16572. 2011
  9. ncbi Differential regulation of the von Willebrand factor and Flt-1 promoters in the endothelium of hypoxanthine phosphoribosyltransferase-targeted mice
    Takashi Minami
    Department of Molecular Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Blood 100:4019-25. 2002
  10. ncbi Decreased GTP-stimulated adenylyl cyclase activity in HPRT-deficient human and mouse fibroblast and rat B103 neuroblastoma cell membranes
    Cibele S Pinto
    Department of Pharmacology and Toxicology, University of Kansas, Lawrence, USA
    J Neurochem 96:454-9. 2006

Detail Information

Publications228 found, 100 shown here

  1. ncbi HPRT-deficient (Lesch-Nyhan) mouse embryos derived from germline colonization by cultured cells
    M Hooper
    Nature 326:292-5. 1987
    ..In human males, HPRT deficiency causes Lesch-Nyhan syndrome, which is characterized by mental retardation and self-mutilation...
  2. pmc Purinergic signaling in human pluripotent stem cells is regulated by the housekeeping gene encoding hypoxanthine guanine phosphoribosyltransferase
    Lina Mastrangelo
    Department of Pediatrics, Center for Neural Circuits and Behavior, University of California at San Diego School of Medicine, La Jolla, CA 92093, USA
    Proc Natl Acad Sci U S A 109:3377-82. 2012
    ..We propose that such mechanisms may play a role in the neuropathology of HPRT-deficiency LND and may point to potential molecular targets for modulation of this intractable neurological phenotype...
  3. pmc MicroRNA-mediated dysregulation of neural developmental genes in HPRT deficiency: clues for Lesch-Nyhan disease?
    Ghiabe Henri Guibinga
    Department of Pediatrics, Center for Neural Circuits and Behavior and Rady Children s Hospital, School of Medicine, University of California San Diego, San Diego, CA 92093 0634, USA
    Hum Mol Genet 21:609-22. 2012
    ..Nevertheless, we propose that these pleiotropic neurodevelopment effects of miR181a may play a role in the pathogenesis of LND...
  4. pmc Mechanism of radiation-induced bystander effect: role of the cyclooxygenase-2 signaling pathway
    Hongning Zhou
    Center for Radiological Research, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 102:14641-6. 2005
    ..These results provide evidence that the COX-2-related pathway, which is essential in mediating cellular inflammatory response, is the critical signaling link for the bystander phenomenon...
  5. pmc Deficiency of the housekeeping gene hypoxanthine-guanine phosphoribosyltransferase (HPRT) dysregulates neurogenesis
    Ghiabe Henri Guibinga
    Department of Pediatrics, Center for Molecular Genetics, University of California, San Diego School of Medicine, La Jolla, California 92093 0634, USA
    Mol Ther 18:54-62. 2010
    ..These results represent direct experimental evidence for aberrant neurogenesis in HPRT deficiency and suggest developmental roles for other housekeeping genes in neurodevelopmental disease...
  6. pmc Hypoxanthine-guanine phosphoribosyl transferase regulates early developmental programming of dopamine neurons: implications for Lesch-Nyhan disease pathogenesis
    Irene Ceballos-Picot
    School of Medicine, Paris Descartes University, 75006 Paris, France
    Hum Mol Genet 18:2317-27. 2009
    ..These results provide novel evidence that HPRT deficiency may affect dopaminergic neurons by influencing early developmental mechanisms...
  7. ncbi HPRT mutants induced in bystander cells by very low fluences of alpha particles result primarily from point mutations
    L Huo
    Department of Cancer Cell Biology, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA
    Radiat Res 156:521-5. 2001
    ..5 cGy involved point mutations, confirming our hypothesis that they are induced by a different mechanism...
  8. pmc HPRT deficiency coordinately dysregulates canonical Wnt and presenilin-1 signaling: a neuro-developmental regulatory role for a housekeeping gene?
    Tae Hyuk Kang
    Department of Pediatrics, Center for Neural Circuit and Behavior and San Diego Rady Children s Hospital, University of California San Diego, San Diego School of Medicine, La Jolla, California, United States of America
    PLoS ONE 6:e16572. 2011
    ....
  9. ncbi Differential regulation of the von Willebrand factor and Flt-1 promoters in the endothelium of hypoxanthine phosphoribosyltransferase-targeted mice
    Takashi Minami
    Department of Molecular Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
    Blood 100:4019-25. 2002
    ..to target the promoters of 2 different genes, namely von Willebrand factor (VWF) and Flt-1, to the hypoxanthine phosphoribosyltransferase (Hprt) gene locus...
  10. ncbi Decreased GTP-stimulated adenylyl cyclase activity in HPRT-deficient human and mouse fibroblast and rat B103 neuroblastoma cell membranes
    Cibele S Pinto
    Department of Pharmacology and Toxicology, University of Kansas, Lawrence, USA
    J Neurochem 96:454-9. 2006
    ..We discuss several possibilities to explain the abnormalities in AC regulation in HPRT deficiency that encompass various species and cell types...
  11. ncbi Impairment of adenylyl cyclase 2 function and expression in hypoxanthine phosphoribosyltransferase-deficient rat B103 neuroblastoma cells as model for Lesch-Nyhan disease: BODIPY-forskolin as pharmacological tool
    Liz Kinast
    Institute of Pharmacology, Medical School of Hannover, Carl Neuberg Str 1, 30625 Hannover, Germany
    Naunyn Schmiedebergs Arch Pharmacol 385:671-83. 2012
    ..We discuss the pathophysiological implications of our data for LND...
  12. pmc Metastasis suppressor NM23-H1 promotes repair of UV-induced DNA damage and suppresses UV-induced melanomagenesis
    Stuart G Jarrett
    Department of Molecular and Biomedical Pharmacology, and Graduate Center for Toxicology, University of Kentucky College of Medicine and Markey Cancer Center, Lexington, Kentucky 40536, USA
    Cancer Res 72:133-43. 2012
    ..Taken together, our data show a critical role for NM23 isoforms in limiting mutagenesis and suppressing UVR-induced melanomagenesis...
  13. pmc Highly efficient transient gene expression and gene targeting in primate embryonic stem cells with helper-dependent adenoviral vectors
    Keiichiro Suzuki
    Division of Gene Therapy, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Saitama 350 1241, Japan
    Proc Natl Acad Sci U S A 105:13781-6. 2008
    ....
  14. ncbi Amphetamine-induced behavioral phenotype in a hypoxanthine-guanine phosphoribosyltransferase-deficient mouse model of Lesch-Nyhan syndrome
    H A Jinnah
    Department of Neurosciences, School of Medicine, University of California, San Diego 92093 0634
    Behav Neurosci 105:1004-12. 1991
    ..This behavioral supersensitivity to amphetamine indicates the existence of an underlying subclinical abnormality of catecholaminergic systems in the brains of HPRT-deficient mice, analogous to findings in human Lesch-Nyhan patients...
  15. pmc Consequences of impaired purine recycling in dopaminergic neurons
    J C Lewers
    Department of Neurology, Meyer Room 6 181, 600 North Wolfe Street, Johns Hopkins University, Baltimore, MD 21287, USA
    Neuroscience 152:761-72. 2008
    ....
  16. ncbi Targeting the Hprt locus in mice reveals differential regulation of Tie2 gene expression in the endothelium
    V Evans
    Massachusetts Institute of Technology, Department of Biology, Cambridge, Massachusetts 02139, USA
    Physiol Genomics 2:67-75. 2000
    To study the in vivo expression of the murine Tie2 gene, we have targeted the hypoxanthine phosphoribosyltransferase (Hprt) gene locus to generate two single-copy transgenic mice: T1, containing the 2,100-bp Tie2 promoter upstream from ..
  17. ncbi DNA double-strand breaks associated with replication forks are predominantly repaired by homologous recombination involving an exchange mechanism in mammalian cells
    C Arnaudeau
    Department of Genetic and Cellular Toxicology, Wallenberg Laboratory, Stockholm University, Stockholm, S-106 91, Sweden
    J Mol Biol 307:1235-45. 2001
    ..We propose that the presence of DSB associated with replication forks rapidly induces HR via an exchange mechanism and that HR plays a more prominent role in the repair of such DSB than does NHEJ...
  18. ncbi Homologous recombination in human embryonic stem cells
    Thomas P Zwaka
    National Primate Research Center and the Department of Anatomy, University of Wisconsin Madison Medical School, Madison, WI 53715, USA
    Nat Biotechnol 21:319-21. 2003
    ..characteristics of human ES cells, that we used to successfully target HPRT1, the gene encoding hypoxanthine phosphoribosyltransferase-1 (HPRT1), and POU5F1, the gene encoding octamer-binding transcription factor 4 (Oct4; also known ..
  19. ncbi Characterization of the dopamine defect in primary cultures of dopaminergic neurons from hypoxanthine phosphoribosyltransferase knockout mice
    D W Smith
    Center for Molecular Genetics, Room 122, Department of Pediatrics, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093 0634, USA
    Mol Ther 1:486-91. 2000
    ..LND) is an X-linked metabolic disorder caused by lack of activity of the purine salvage enzyme hypoxanthine phosphoribosyltransferase (HPRT) and characterized by hyperuricemia and debilitating neurological manifestations...
  20. ncbi Tissue-specific expression of a BAC transgene targeted to the Hprt locus in mouse embryonic stem cells
    Jason D Heaney
    Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine H166, 500 University Drive, Hershey, PA 17033 0850, USA
    Genomics 83:1072-82. 2004
    The hypoxanthine phosphoribosyltransferase (Hprt) locus has been shown to have minimal influence on transgene expression when used as a surrogate site in the mouse genome...
  21. ncbi HPRT: gene structure, expression, and mutation
    J T Stout
    Annu Rev Genet 19:127-48. 1985
  22. ncbi The spectrum of inherited mutations causing HPRT deficiency: 75 new cases and a review of 196 previously reported cases
    H A Jinnah
    Department of Neurology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA
    Mutat Res 463:309-26. 2000
    ....
  23. pmc A Functional chromatin domain does not resist X chromosome inactivation: silencing of cLys correlates with methylation of a dual promoter-replication origin
    Suyinn Chong
    Division of Biology, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA
    Mol Cell Biol 22:4667-76. 2002
    ....
  24. ncbi Production of a model for Lesch-Nyhan syndrome in hypoxanthine phosphoribosyltransferase-deficient mice
    C L Wu
    Institute of Cell and Molecular Biology, Edinburgh University, Scotland
    Nat Genet 3:235-40. 1993
    The inherited disease Lesch-Nyhan syndrome, which is caused by a deficiency of the enzyme hypoxanthine phosphoribosyltransferase (HPRT), is characterized by behavioural alterations, including self-injurious behaviour and mental ..
  25. ncbi Study of the adenosinergic system in the brain of HPRT knockout mouse (Lesch-Nyhan disease)
    Matteo Bertelli
    Laboratorio di Genetica Medica, Istituto Malattie Rare Mauro Baschirotto BIRD Foundation Onlus, 36023 Costozza, Vicenza, Italy
    Clin Chim Acta 373:104-7. 2006
    ..Altered adenosine transport across the membrane of HPRT-deficient lymphocytes has been reported, suggesting adenosine involvement in LND...
  26. ncbi Mutation induction by different types of radiation at the Hprt locus
    J Kiefer
    Strahlenzentrum der Justus Liebig Universität, Giessen, Germany
    Mutat Res 431:429-48. 1999
    ..Based on a total number of 134 X-ray- and 192 alpha-induced mutants, it is concluded that the total fraction of mutant clones without deletions (partial or total) is about 40% for X-rays and only about 20% for alpha-particles...
  27. pmc Development of a markerless genetic exchange method for Methanosarcina acetivorans C2A and its use in construction of new genetic tools for methanogenic archaea
    Matthew A Pritchett
    Department of Microbiology, University of Illinois at Urbana Champaign, Urbana, Illinois 61801, USA
    Appl Environ Microbiol 70:1425-33. 2004
    ..Mutants with lesions in the hpt gene, encoding hypoxanthine phosphoribosyltransferase, were shown to be >35-fold more resistant to the toxic base analog 8-aza-2,6-diaminopurine (8ADP) ..
  28. ncbi Validation of the human T-lymphocyte cloning assay--ring test report from the EU concerted action on HPRT mutation (EUCAHM)
    S M Hou
    Karolinska Institute, Department of Biosciences, CNT Novum, Huddinge, Sweden
    Mutat Res 431:211-21. 1999
    ..This modified UOP needs to be further evaluated in order to be used for future databases on HPRT MFs in various populations...
  29. pmc Functional copies of a human gene can be directly isolated by transformation-associated recombination cloning with a small 3' end target sequence
    N Kouprina
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Proc Natl Acad Sci U S A 95:4469-74. 1998
    ..TAR cloning vector was constructed that, when linearized, contained a small amount (381 bp) of 3' hypoxanthine phosphoribosyltransferase (HPRT) sequence at one end and an 189-bp Alu repeat at the other end...
  30. ncbi Molecular characterization of two deletion events involving Alu-sequences, one novel base substitution and two tentative hotspot mutations in the hypoxanthine phosphoribosyltransferase (HPRT) gene in five patients with Lesch-Nyhan syndrome
    T Tvrdik
    Department of Molecular Medicine, The Karolinska Hospital, Stockholm, Sweden
    Hum Genet 103:311-8. 1998
    Mutations identified in the hypoxanthine phosphoribosyltransferase (HPRT) gene of patients with Lesch-Nyhan (LN) syndrome are dominated by simple base substitutions...
  31. ncbi Lack of mutagenicity of chromium picolinate in the hypoxanthine phosphoribosyltransferase gene mutation assay in Chinese hamster ovary cells
    Ronald S Slesinski
    ENVIRON Health Sciences Institute, 4350 North Fairfax Drive, Suite 300, Arlington, VA 22203, USA
    Mutat Res 585:86-95. 2005
    ..A previous study reported that CrPic produced increases in mutations of the hypoxanthine phosphoribosyltransferase (Hprt) gene in Chinese hamster ovary (CHO) cell mutation tests...
  32. ncbi Appropriate tissue- and cell-specific expression of a single copy human angiotensinogen transgene specifically targeted upstream of the HPRT locus by homologous recombination
    B Cvetkovic
    Molecular Biology Interdisciplinary Program, The University of Iowa College of Medicine, Iowa City, Iowa 52242, USA
    J Biol Chem 275:1073-8. 2000
    ..We establish the validity of this approach by showing that the hAGT(hprt) mice have normal tissue- and cell-specific expression of the human angiotensinogen gene and normally produce and process the hAGT protein at physiological levels...
  33. ncbi Altered membrane NTPase activity in Lesch-Nyhan disease fibroblasts: comparison with HPRT knockout mice and HPRT-deficient cell lines
    Cibele S Pinto
    Department of Pharmacology and Toxicology, University of Kansas, Lawrence, Kansas, USA
    J Neurochem 93:1579-86. 2005
    ..Thus, future studies on biochemical changes in LND should be conducted in parallel in several HPRT-deficient systems...
  34. ncbi HPRT mutations in humans: biomarkers for mechanistic studies
    R J Albertini
    University of Vermont Genetic Toxicology Laboratory, 32 North Prospect Street, Burlington, VT 05401, USA
    Mutat Res 489:1-16. 2001
    ..Most recently, HPRT is finding use in studies of in vivo selection for in vivo mutations arising in either somatic or germinal cells...
  35. pmc Interfering RNA-mediated purine analog resistance for in vitro and in vivo cell selection
    Christopher C Porter
    Rick Wilson Center for Cancer and Blood Disorders, The Children s Hospital, Aurora, CO, USA
    Blood 112:4466-74. 2008
    ..These findings indicate that iPAR/6TG can be used for in vivo hematopoietic progenitor cell selection...
  36. pmc Molecular analysis of a female Lesch-Nyhan patient
    N Ogasawara
    Department of Biochemistry, Central Hospital, Aichi, Japan
    J Clin Invest 84:1024-7. 1989
    We report the identification of a female patient with the X-linked recessive Lesch-Nyhan syndrome (hypoxanthine phosphoribosyltransferase [HPRT] deficiency)...
  37. ncbi Multiplex fluorescent RT-PCR to quantify leukemic fusion transcripts
    M Dupont
    Laboratoire de Génétique Moleculaire et Chromosomique, Hĵpital Arnaud de Villeneuve, CNRS, Montpellier, France
    Biotechniques 33:158-60, 162, 164. 2002
    ..We demonstrate that our novelfluorescent method is useful to detect and quantify residual leukemic cells in patients undergoing therapy...
  38. ncbi Multiplex DNA deletion detection and exon sequencing of the hypoxanthine phosphoribosyltransferase gene in Lesch-Nyhan families
    R A Gibbs
    Institute for Molecular Genetics, Howard Hughes Medical Institute, Houston, Texas
    Genomics 7:235-44. 1990
    ..is a genetically lethal human neurological disease that results from mutations that inactivate the hypoxanthine phosphoribosyltransferase (HPRT) gene...
  39. ncbi Gene expression and mRNA editing of serotonin receptor 2C in brains of HPRT gene knock-out mice, an animal model of Lesch-Nyhan disease
    Matteo Bertelli
    Laboratory of Molecular Genetics, International Association of Medical Genetics, Trento, Italy
    J Clin Neurosci 16:1061-3. 2009
    ..The above alteration found in HPRT-deficient mice is similar to those found in other animal models used to study aggressive and self-injurious behaviour...
  40. ncbi Structural and functional analysis of mutations at the human hypoxanthine phosphoribosyl transferase (HPRT1) locus
    Jianxin Duan
    Department of Biosciences at Novum, Center for Structural Biochemistry, Karolinska Institutet, Huddinge, Sweden
    Hum Mutat 23:599-611. 2004
    ..We have also noticed a strong correlation between mutations in the tetramer interfaces and observed phenotypes, suggesting a functional role for a tetramer transition during catalysis...
  41. pmc Influence of sex, smoking and age on human hprt mutation frequencies and spectra
    J Curry
    Centre for Environmental Health and the Department of Biology, University of Victoria, Victoria, British Columbia V8W 3N5, Canada
    Genetics 152:1065-77. 1999
    ..There is no indication of a significant shift in mutational spectra with age for individuals older than 19 yr, with the exception of A:T --> C:G transversions. These events are recovered more frequently in older individuals...
  42. pmc Modelling human regulatory variation in mouse: finding the function in genome-wide association studies and whole-genome sequencing
    Jean Francois Schmouth
    Centre for Molecular Medicine and Therapeutics at the Child and Family Research Institute, University of British Columbia, Vancouver, Canada
    PLoS Genet 8:e1002544. 2012
    ....
  43. pmc Role of the promoter in maintaining transcriptionally active chromatin structure and DNA methylation patterns in vivo
    Sung Hae Lee Kang
    Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, Florida 32610, USA
    Mol Cell Biol 23:4150-61. 2003
    ..These findings suggest that the promoter and active transcription play a relatively limited role in maintaining transcriptionally potentiated epigenetic states...
  44. ncbi Differential expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), beta actin and hypoxanthine phosphoribosyltransferase (HPRT) in postnatal rabbit sclera
    T K Moe
    Singapore Eye Research Institute, Singapore
    Curr Eye Res 23:44-50. 2001
    ..This study demonstrates that 18S rRNA may be preferable to normalize genes of interest in studies of early development...
  45. ncbi Targeted gene knockout by 2'-O-aminoethyl modified triplex forming oligonucleotides
    N Puri
    NIA, National Institutes of Health, Baltimore, Maryland 21224, USA
    J Biol Chem 276:28991-8. 2001
    ..We conclude that the AE modification can enhance the biological activity of pyrimidine TFOs, but that extensive substitution is deleterious...
  46. ncbi Mapping of an origin of DNA replication near the transcriptional promoter of the human HPRT gene
    Stephanie M Cohen
    Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7525, USA
    J Cell Biochem 85:346-56. 2002
    ..5 kb upstream of a previously reported autonomously replicating sequence (Sykes et al. [1988] Mol. Gen. Genet. 212:301-309)...
  47. ncbi Benzo[a]pyrene diol epoxide-deoxyguanosine adducts are accurately bypassed by yeast DNA polymerase zeta in vitro
    Srilatha Simhadri
    Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, College of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ 08854 8020, USA
    Mutat Res 508:137-45. 2002
    ..This corresponds to a probability of mutation lower than 0.3%, the limit of detection, and demonstrates the remarkable fidelity of yeast pol zeta in translesion synthesis past these BP DB-dG lesions in vitro...
  48. pmc Isolation and characterization of a full-length expressible cDNA for human hypoxanthine phosphoribosyl transferase
    D J Jolly
    Proc Natl Acad Sci U S A 80:477-81. 1983
    We have cloned a full-length 1.6-kilobase cDNA of a human mRNA coding for hypoxanthine phosphoribosyltransferase (HPRT; IMP:pyrophosphate phosphoribosyltransferase, EC 2.4.2...
  49. ncbi Decelerated rate of dendrite outgrowth from dopaminergic neurons in primary cultures from brains of hypoxanthine phosphoribosyltransferase-deficient knockout mice
    P Boer
    Felsenstein Medical Research Center, Rabin Medical Center, Petah Tikva, Israel
    Neurosci Lett 303:45-8. 2001
    Lesch-Nyhan syndrome (LNS), caused by the complete deficiency of hypoxanthine phosphoribosyltransferase (HPRT), is characterized by a neurological deficit, the etiology of which is still unclear...
  50. ncbi A Golgi study of neuronal architecture in a genetic mouse model for Lesch-Nyhan disease
    Ivan Mikolaenko
    Department of Neurology, Meyer Room 6 181, Johns Hopkins Hospital, Baltimore, MD 21287, USA
    Neurobiol Dis 20:479-90. 2005
    ..These findings demonstrate that HPRT deficiency is associated with changes in neuronal architecture in the HPRT- mice. Similar abnormalities in the LND brain could underlie some of the clinical manifestations...
  51. pmc Selection of reference genes for quantitative real-time PCR in a rat asphyxial cardiac arrest model
    Kristina Langnaese
    Institute of Medical Neurobiology, University of Magdeburg, Leipziger Str, 44, D 39120 Magdeburg, Germany
    BMC Mol Biol 9:53. 2008
    ..Moreover, experimental groups treated with the anti-inflammatory and anti-apoptotic drug minocycline have been included in the study as well...
  52. pmc Repression of mutagenesis by Rad51D-mediated homologous recombination
    John M Hinz
    Biosciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA 94551, USA
    Nucleic Acids Res 34:1358-68. 2006
    ....
  53. pmc Single-copy transgenic mice with chosen-site integration
    S K Bronson
    Department of Pathology, University of North Carolina, Chapel Hill 27599 7525, USA
    Proc Natl Acad Sci U S A 93:9067-72. 1996
    ..promoter or a human beta-actin promoter has been inserted immediately 5' to the X-linked hypoxanthine phosphoribosyltransferase locus by a directly selectable homologous recombination event...
  54. ncbi Regulation of hypoxanthine phosphoribosyltransferase, glyceraldehyde-3-phosphate dehydrogenase and beta-actin mRNA expression in porcine immune cells and tissues
    D L Foss
    Department of Veterinary Pathobiology, University of Minnesota, St Paul 55108, USA
    Anim Biotechnol 9:67-78. 1998
    ..The expression of hypoxanthine phosphoribosyltransferase (HPRT) was detected only by northern hybridization of poly-A+ enriched RNA and by reverse ..
  55. ncbi A combinatorial network of evolutionarily conserved myelin basic protein regulatory sequences confers distinct glial-specific phenotypes
    Hooman F Farhadi
    Royal Victoria Hospital, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec H3A 1A1, Canada
    J Neurosci 23:10214-23. 2003
    ....
  56. ncbi Importance of clustered 2'-O-(2-aminoethyl) residues for the gene targeting activity of triple helix-forming oligonucleotides
    Nitin Puri
    Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA
    Biochemistry 43:1343-51. 2004
    ..Under these circumstances, TFOs with faster on rates would be favored because they would be more likely to be in triplexes at the time of photoactivation...
  57. pmc Brca2 (XRCC11) deficiency results in radioresistant DNA synthesis and a higher frequency of spontaneous deletions
    Maria Kraakman-van der Zwet
    Department of Radiation Genetics and Chemical Mutagenesis MGC, Leiden University Medical Center, The Netherlands
    Mol Cell Biol 22:669-79. 2002
    ....
  58. ncbi Pms2 deficiency results in increased mutation in the Hprt gene but not the Tk gene of Tk(+/-) transgenic mice
    Vasily N Dobrovolsky
    Division of Genetic and Reproductive Toxicology, HFT 120, National Center for Toxicological Research, 3900 NCTR Road, Jefferson, AR 72079, USA
    Mutagenesis 18:365-70. 2003
    ..The interaction between Tk deficiency and a component of the MMR system suggests that Tk-deficient cells may have higher levels of DNA polymerase misincorporation or endogenous DNA damage than Tk-proficient cells...
  59. ncbi Neurocognitive functioning in Lesch-Nyhan disease and partial hypoxanthine-guanine phosphoribosyltransferase deficiency
    D J Schretlen
    Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    J Int Neuropsychol Soc 7:805-12. 2001
    ..The variants produced scores that were intermediate between those of patients with LND and normal participants on nearly every cognitive measure. We discuss these findings in terms of what is known about the neuropathology of LND...
  60. ncbi hREV3 is essential for error-prone translesion synthesis past UV or benzo[a]pyrene diol epoxide-induced DNA lesions in human fibroblasts
    Ziqiang Li
    Carcinogenesis Laboratory, Department of Microbiology and Molecular Genetics, Food Safety and Toxicology Building, Michigan State University, East Lansing, MI 48824 1302, USA
    Mutat Res 510:71-80. 2002
    ..However, the conclusion is supported by the fact that in a similar study with a strain expressing a high level of antisense hREV1, a very similar result was obtained, i.e. UV or BPDE mutagenesis was virtually eliminated...
  61. ncbi In vivo pattern of lipopolysaccharide and anti-CD3-induced NF-kappa B activation using a novel gene-targeted enhanced GFP reporter gene mouse
    Scott T Magness
    Department of Medicine, University of North Carolina, Chapel Hill, NC 27599, USA
    J Immunol 173:1561-70. 2004
    ..was used to insert a single copy of a NF-kappa B-dependent EGFP reporter gene 5' of the X-linked hypoxanthine phosphoribosyltransferase locus in mouse embryonic stem cells...
  62. ncbi Next generation tools for high-throughput promoter and expression analysis employing single-copy knock-ins at the Hprt1 locus
    G S Yang
    Canada s Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, British Columbia, Canada
    Genomics 93:196-204. 2009
    ..We have validated our tools as part of the Pleiades Promoter Project (http://www.pleiades.org), with the generation of brain-specific EGFP positive germline mouse strains...
  63. ncbi Tissue selective expression of conditionally-regulated ROCK by gene targeting to a defined locus
    Michael S Samuel
    The Beatson Institute for Cancer Research, Glasgow, United Kingdom
    Genesis 47:440-6. 2009
    ..K14-ROCKII:mER mice will be valuable for examining the role of ROCK in skin development and cancer...
  64. pmc Selection of reference genes for gene expression studies in human neutrophils by real-time PCR
    Xiaozhu Zhang
    The James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, St, Paul s Hospital, University of British Columbia, Vancouver, Canada
    BMC Mol Biol 6:4. 2005
    ..Thus the selection of reference gene(s) is critical for gene expression studies. For this purpose, 10 commonly used housekeeping genes were investigated in isolated human neutrophils...
  65. ncbi Modeling for Lesch-Nyhan disease by gene targeting in human embryonic stem cells
    Achiya Urbach
    Department of Genetics, Silberman Institute of Life Science, The Hebrew University, Givat Ram, Jerusalem 91904, Israel
    Stem Cells 22:635-41. 2004
    ..We therefore suggest that human diseases may be modeled using human ES cells...
  66. ncbi Role of neuronal nitric oxide in the dopamine deficit of HPRT-deficient mice
    Doug W Smith
    Center for Molecular Genetics, Department of Pediatrics, University of California, San Diego, CA, USA
    Metab Brain Dis 22:39-43. 2007
    ..Basal ganglia dopamine deficits manifest in both patients and hypoxanthine phosphoribosyltransferase (HPRT) mutant mice...
  67. ncbi Gene mutations with characteristic deletions in cord blood T lymphocytes associated with passive maternal exposure to tobacco smoke
    B A Finette
    Department of Pediatrics, University of Vermont, Burlington 05405, USA
    Nat Med 4:1144-51. 1998
    ..Recent epidemiological studies of maternal and paternal cigarette smoke exposure and childhood cancers may need to be re-interpreted, given these results...
  68. pmc Localization of loci for hypoxanthine phosphoribosyltransferase and glucose-6-phosphate dehydrogenase and biochemical evidence of nonrandom X chromosome expression from studies of a human X-autosome translocation
    G S Pai
    Proc Natl Acad Sci U S A 77:2810-3. 1980
    ..The break point on the X chromosome, at the junction of Xq27-Xq28, separates the loci for hypoxanthine phosphoribosyltransferase (HPRT) and G6PD...
  69. ncbi Automated DNA sequencing of the human HPRT locus
    A Edwards
    Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030
    Genomics 6:593-608. 1990
    ..005) and those sequences in the latter half of the locus oriented randomly (5'----3' = 67%, P less than 0.5). The development and performance of the sequencing strategy and the features of the human HPRT gene are presented...
  70. ncbi Tissue-specific aberrations of gene expression in HPRT-deficient mice: functional complexity in a monogenic disease?
    Shaochun Song
    Department of Pediatrics, University of California, San Diego School of Medicine, La Jolla, California 92093, USA
    Mol Ther 15:1432-43. 2007
    ..Knowledge of these secondary genetic defects may help in the identification of targets for drug- and gene-based therapy...
  71. ncbi Sequential genetic modification of the hprt locus in human ESCs combining gene targeting and recombinase-mediated cassette exchange
    Alexandra I Di Domenico
    Division of Gene Function and Development, Roslin Institute Edinburgh, Roslin, EH25 9PS, UK
    Cloning Stem Cells 10:217-30. 2008
    ..Finally, we report a double replacement strategy using two sequential gene targeting steps resulting in the targeted correction of an hprt-mutated hESC line...
  72. ncbi Dopamine deficiency in a genetic mouse model of Lesch-Nyhan disease
    H A Jinnah
    Department of Neurosciences, University of California San Diego School of Medicine, La Jolla 92093
    J Neurosci 14:1164-75. 1994
    ..These results indicate that HPRT deficiency is associated with a relatively specific deficit in basal ganglia dopamine systems that emerges during the first 2 months of postnatal development...
  73. pmc Plasma membrane calcium ATPase (PMCA4): a housekeeper for RT-PCR relative quantification of polytopic membrane proteins
    Anna Maria Calcagno
    Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, DHHS, Bethesda, MD 20892 42546, USA
    BMC Mol Biol 7:29. 2006
    ....
  74. pmc Selection of housekeeping genes for gene expression studies in the adult rat submandibular gland under normal, inflamed, atrophic and regenerative states
    Nicholas Silver
    Salivary Research Unit, Floor 17, Guy s Tower, King s College London, London, UK
    BMC Mol Biol 9:64. 2008
    ..For the purpose of this study, 7 commonly used housekeeping genes were investigated in salivary submandibular glands under normal, inflamed, atrophic and regenerative states...
  75. ncbi Behavioral and neurochemical evaluation of a transgenic mouse model of Lesch-Nyhan syndrome
    S Finger
    Department of Experimental Psychology, University of Cambridge, U K
    J Neurol Sci 86:203-13. 1988
    ..In contrast to Lesch-Nyhan children, mice may be able to utilize alternative pathways more effectively to maintain purine and neurotransmitter levels within the ranges required for normal brain development and function...
  76. ncbi Structural and functional studies of the human phosphoribosyltransferase domain containing protein 1
    Martin Welin
    Structural Genomics Consortium, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
    FEBS J 277:4920-30. 2010
    ..The data obtained in the present study indicate that PRTFDC1 does not have a direct catalytic role in the nucleotide salvage pathway...
  77. ncbi HPRT-APRT-deficient mice are not a model for lesch-nyhan syndrome
    S J Engle
    Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis 46202 5251, USA
    Hum Mol Genet 5:1607-10. 1996
    ..Thus, APRT-HPRT-deficient mice, which are devoid of any purine salvage pathways, show no novel phenotype and are not a model for the behavioral abnormalities associated with the Lesch-Nyhan syndrome as previously suggested...
  78. ncbi Decreased frequency and highly aberrant spectrum of ultraviolet-induced mutations in the hprt gene of mouse fibroblasts expressing antisense RNA to DNA polymerase zeta
    Marilyn Diaz
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC, USA
    Mol Cancer Res 1:836-47. 2003
    ..The antisense Rev3 mice should be a useful model to study mutagenic lesion bypass by pol zeta in mammalian cells and to investigate the role this polymerase plays in carcinogenesis...
  79. ncbi Functional organization of a Schwann cell enhancer
    Eric Denarier
    Laboratory of Developmental Biology, Molecular Oncology Group H 5, McGill University Health Centre, Montreal, Quebec, H3A 1A1, Canada
    J Neurosci 25:11210-7. 2005
    ..motifs were introduced into reporter constructs that were inserted in single copy at a common hypoxanthine phosphoribosyltransferase docking site in embryonic stem cells...
  80. ncbi HPRT mutations, TCR gene rearrangements, and HTLV-1 integration sites define in vivo T-cell clonal lineages
    Mark Allegretta
    Department of Pathology, University of Vermont, Burlington, Vermont 05405, USA
    Environ Mol Mutagen 45:326-37. 2005
    ..Lineage reconstruction of an in vivo proliferating HPRT mutant clone allows timing of the integration event to a postthymic differentiated cell prior to the occurrence of HPRT mutations...
  81. ncbi Gene duplication and inactivation in the HPRT gene family
    Alaine C Keebaugh
    Department of Human Genetics, School of Medicine, Atlanta, GA 30322, USA
    Genomics 89:134-42. 2007
    b>Hypoxanthine phosphoribosyltransferase (HPRT1) is a key enzyme in the purine salvage pathway, and mutations in HPRT1 cause Lesch-Nyhan disease...
  82. ncbi Engineering chromosomal rearrangements in mice
    Y Yu
    Program in Developmental Biology, Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030
    Nat Rev Genet 2:780-90. 2001
    ....
  83. pmc A genetic system for direct selection of gene-positive clones during recombinational cloning in yeast
    Vladimir Noskov
    Laboratory of Biosystems and Cancer, National Cancer Institute, NIH, Building 37, Room 5032, Bethesda, MD 20892 4264, USA
    Nucleic Acids Res 30:E8. 2002
    ..This method produces positive YAC recombinants at a frequency of approximately 40%. This novel TAR cloning method provides a powerful tool for structural and functional analysis of complex genomes...
  84. pmc Lack of increased genetic damage in 1,3-butadiene-exposed Chinese workers studied in relation to EPHX1 and GST genotypes
    Luoping Zhang
    School of Public Health, University of California, 140 Warren Hall, Berkeley, CA 94720 7360, USA
    Mutat Res 558:63-74. 2004
    ..Together, these studies suggest that low levels of occupational BD exposure do not pose a significant risk of genetic damage...
  85. ncbi Alternative IMP binding in feedback inhibition of hypoxanthine-guanine phosphoribosyltransferase from Thermoanaerobacter tengcongensis
    Qiang Chen
    Laboratory of Structural Biology, College of Life Sciences, Peking University, Beijing 100871, People s Republic of China
    J Mol Biol 348:1199-210. 2005
    ..tengcongensis HGPRT is compared with those of mesophilic HPRTs, and several possible features contributing to its thermostability are elucidated. Overall, T.tengcongensis HGPRT appears to be more diverged from other PRTs...
  86. ncbi Lesch-Nyhan disease in a female with a clinically normal monozygotic twin
    Laura De Gregorio
    University of California San Diego, La Jolla, CA 92093, USA
    Mol Genet Metab 85:70-7. 2005
    ..As in many other reported cases of X-linked diseases, the discordant phenotype of the two monozygous twin sisters suggests that the process responsible for monozygotic twinning can trigger skewed X inactivation...
  87. ncbi Mutation carrier testing in Lesch-Nyhan syndrome families: HPRT mutant frequency and mutation analysis with peripheral blood T lymphocytes
    J Patrick O'Neill
    Genetics Laboratory, University of Vermont, Burlington, VT 05401, USA
    Genet Test 8:51-64. 2004
    ..This approach provides a rapid assay that yields information on carrier status within 10 days of sample receipt...
  88. ncbi Targeted gene correction of hprt mutations by 45 base single-stranded oligonucleotides
    Oliver Kenner
    Department of Human Genetics, University of Ulm, Albert Einstein Allee 11, D 89070 Ulm, Germany
    Biochem Biophys Res Commun 299:787-92. 2002
    ..The correction efficiency was very low but reproducible. We suggest that this system allows one to investigate targeted gene correction in dependence on the target sequence and the oligonucleotides used...
  89. ncbi Minimum number of 2'-O-(2-aminoethyl) residues required for gene knockout activity by triple helix forming oligonucleotides
    Nitin Puri
    Laboratory of Molecular Gerontology, National Institutes on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA
    Biochemistry 41:7716-24. 2002
    ..The HPRT knockout frequencies with the most active TFOs were 300-400-fold above the background, whereas there was no activity against the APRT gene, a monitor of nonspecific mutagenesis...
  90. ncbi Molecular, biochemical, and genetic characterization of a female patient with Lesch-Nyhan disease
    Choni Rinat
    Division of Pediatric Nephrology, Shaare Zedek Medical Center, P O Box 3235, Jerusalem 91031, Israel
    Mol Genet Metab 87:249-52. 2006
    ..disorder caused by virtually complete deficiency of activity of the purine salvage enzyme hypoxanthine phosphoribosyltransferase (HPRT; EC 2.4.2.8)...
  91. ncbi Pseudogenes of the human HPRT1 gene
    Janice A Nicklas
    Department of Pediatrics, University of Vermont, Burlington, Vermont, USA
    Environ Mol Mutagen 47:212-8. 2006
    ..This gene with unknown function is almost completely homologous to HPRT1 in exon structure (except for a 21 bp (seven amino acid) insertion in exon 1) and 68% homologous in amino acid sequence...
  92. ncbi Hypoxanthine decreases equilibrative type of adenosine transport in lymphocytes from Lesch-Nyhan patients
    C Prior
    Laboratório de Bioquímica Clínica, La Paz University Hospital, Paseo Castellana 261, Madrid, Spain
    Eur J Clin Invest 37:905-11. 2007
    ..The aim of this study was to determine adenosine transporter subtypes affected by HPRT deficiency and by the associated hypoxanthine excess...
  93. ncbi Effects of aging, dietary restriction and glucocorticoid treatment on housekeeping gene expression in rat cortex and hippocampus-evaluation by real time RT-PCR
    Nikola Tanic
    Institute for Biological Research, Bul Despota Stefana 142, 11 060 Belgrade, Serbia
    J Mol Neurosci 32:38-46. 2007
    ..Our results demonstrate the importance of the right choice of HKG and suggest the appropriate endogenous control to be used for TaqMan RT-PCR analysis of mRNA expression in rat cortex and hippocampus for selected experimental paradigms...
  94. ncbi Electrophysiological characteristics of limbic and motor globus pallidus internus (GPI) neurons in two cases of Lesch-Nyhan syndrome
    E Pralong
    UNN NS BH 13, CHUV, 1011 Lausanne, Switzerland
    Neurophysiol Clin 35:168-73. 2005
    ..In order to shed light on the pathophysiology of dystonia, we report the pallidal electrophysiological activity recorded in two patients during deep brain stimulation surgery (DBS)...
  95. ncbi A human neuronal tissue culture model for Lesch-Nyhan disease
    Thomas L Shirley
    Department of Neurology, Johns Hopkins University, Baltimore, Maryland, USA, and Department of Biology, Necker Enfants Malades Hospital, Paris, France
    J Neurochem 101:841-53. 2007
    ..These cells combine the analytical power of multiple lines and a human, neuronal origin to provide an important tool to investigate the pathophysiology of HPRT deficiency...
  96. ncbi Molecular epidemiological studies in 1,3-butadiene exposed Czech workers: female-male comparisons
    Richard J Albertini
    BioMosaics, Inc, 665 Spear Street, Burlington, VT 05401, USA
    Chem Biol Interact 166:63-77. 2007
    ..However, as in the first, differences in the metabolic detoxification of BD as reflected in relative amounts of the M1 and M2 urinary metabolites were associated with genotypes, this time both GST and EH...
  97. pmc Selection of housekeeping genes for gene expression studies in human reticulocytes using real-time PCR
    Nicholas Silver
    Molecular Haematology, Division of Gene and Cell Based Therapy, King s College London School of Medicine at King s College Hospital, Denmark Hill, London, SE5 9PJ, UK
    BMC Mol Biol 7:33. 2006
    ..On this basis, stability of the candidate housekeeping genes was ranked according to repeatability of the gene expression differences among 31 samples...
  98. pmc Assessment of 1,3-butadiene exposure in polymer production workers using HPRT mutations in lymphocytes as a biomarker
    M M Ammenheuser
    Division of Environmental Toxicology, Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, Texas 77555-1110, USA
    Environ Health Perspect 109:1249-55. 2001
    ..4 and 0.6. The correlations among BD exposure and the biomarkers of internal exposure and genotoxicity suggest that occupational exposure to BD, in the range of 1-3 ppm, may be associated with adverse biological effects...
  99. ncbi Assessment of purine-dopamine interactions in 6-hydroxydopamine-lesioned rats: evidence for pre- and postsynaptic influences by adenosine
    H Criswell
    Department of Psychiatry, School of Medicine, University of North Carolina, Chapel Hill
    J Pharmacol Exp Ther 244:493-500. 1988
    ..Relative potencies of the adenosine agonists for A1 and A2-adenosine receptors suggested involvement of an A2-adenosine receptor in this action.(ABSTRACT TRUNCATED AT 250 WORDS)..
  100. ncbi Targeting of human eNOS promoter to the Hprt locus of mice leads to tissue-restricted transgene expression
    P V Guillot
    Beth Israel Deaconess Medical Center, Department of Molecular Medicine, Boston 02215, USA
    Physiol Genomics 2:77-83. 2000
    ..nitric oxide synthase (eNOS) promoter coupled to the LacZ reporter gene to the X-linked hypoxanthine phosphoribosyltransferase (Hprt) locus of mice by homologous recombination...
  101. ncbi Inactivation of the mouse HPRT locus by a 203-bp retroposon insertion and a 55-kb gene-targeted deletion: establishment of new HPRT-deficient mouse embryonic stem cell lines
    H Tsuda
    Cell Genesys, Inc, Foster City, California 94404, USA
    Genomics 42:413-21. 1997
    ..The second approach resulted in a 55-kb deletion of the mouse HPRT locus, demonstrating the feasibility of replacement-targeting vectors to generate large genomic DNA deletions...

Research Grants62

  1. Genetic Analysis of Purine Metabolism in Leishmania donovani
    Buddy Ullman; Fiscal Year: 2013
    ..These proteins include: ADSS, ASL, GMP synthetase, the three phosphoribosylpyrophosphate synthetases, and the peroxisomal-like nucleotide translocase homolog. ..
  2. PURINE BOTTLENECKS FOR THE CHEMOTHERAPY OF TOXOPLASMOSIS
    ELMER PFEFFERKORN; Fiscal Year: 1999
    ..The investigators view the primary goal of this proposal to be the definitive characterization of those steps in toxoplasma purine metabolism that are targets for the chemotherapy of toxoplasmosis. ..
  3. MUTATIONAL ANALYSIS OF A PARASITE PURINE SALVAGE ENZYME
    SYDNEY CRAIG; Fiscal Year: 2001
    ..The enzyme that is the subject of this study is the hypoxanthine phosphoribosyltransferase (HPRT) of Trypanosoma cruzi, etiologic agent of Chagas' disease...
  4. MOLECULAR GENETIC ANALYSIS OF XQ28
    Stephen Warren; Fiscal Year: 1992
    ....
  5. MECHANISM OF METAL ANTAGONISTIC EFFECT ON BPDE MUTANTS
    DAVID REINHOLD; Fiscal Year: 1999
    ..diol epoxide (BPDE), all common environmental carcinogens, on the mutant frequency of the hypoxanthine phosphoribosyltransferase (HPRT) gene in normal human fibroblasts...
  6. CRYSTAL STRUCTURE OF TOXOPLASMA GONDII HGPRT
    DAVID BORHANI; Fiscal Year: 1999
    ....
  7. PURINE METABOLISM IN SCHISTOSOMA MANSONI
    C Wang; Fiscal Year: 1991
    ..mansoni which has a unique substrate specificity and is the target of the potent antischistosomal activity of tubercidin. We plan to further characterize this enzyme as a potential target for antischistosomal chemotherapy...
  8. GENOTOXICITY OF BENZO[A]PYRENE DERIVATIVES AND SULFITE
    Gregory Reed; Fiscal Year: 1993
    ....
  9. Lesch-Nyhan disease: dissecting the functions of HGprt
    HYDER JINNAH; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  10. STRUCTURAL ANALYSIS OF THE HGPRT FROM TRYPANOSOMA CRUZI
    ANN EAKIN; Fiscal Year: 2001
    ....
  11. RADIATION GENOTOXICITY FROM THE CHERNOBYL ACCIDENT
    IRENE JONES; Fiscal Year: 1999
    ..detected by fluorescence in situ hybridization; 2) glycophorin A mutation in erythrocytes; and 3) hypoxanthine phosphoribosyltransferase (HPRT) mutation in lymphocytes...
  12. Gene engineering of nerve stem using HSV amplicon vector
    Yoshinaga Saeki; Fiscal Year: 2003
    ..further understanding of HSV/EBV/genomic vectors and confirm the advantages of genomic transgenes and EBV elements, which then should provide a strong basis for genetic engineering of NSCs using HSV/EBV/genomic vectors ..
  13. MECHANISMS OF DNA DEPENDENT CYTOTOXICITY BY CHEMICALS
    JOE GRISHAM; Fiscal Year: 1992
    ..In addition, the breakdown of DNA in affected cells will be examined by pulsed field and conventional gel electrophoresis...
  14. INBORN ERRORS OF A PURINE SALVAGE PATHWAY
    Jay Tischfield; Fiscal Year: 2000
    ..A study of DHA-induced gene expression in cultured kidney epithelial cells and whole kidneys is aimed at understanding molecular genetic processes that lead to nephrolithiasis and kidney failure. ..
  15. Structural Dissection of the HGPRT Reaction Mechanism
    DAVID BORHANI; Fiscal Year: 2001
    ..Prof. Charles Grubmeyer will perform single-turnover kinetics studies of wildtype and mutant T. gondii HGPRTs. Prof. Herbert Cheung will consult on fluorescence studies. ..
  16. MURINE MODEL OF CAG REPEAT DISEASES
    Roger Albin; Fiscal Year: 2002
    ..by inserting a 146 unit CAG repeat disorders by inserting a 146 unit CAG repeat into the murine hypoxanthine phosphoribosyltransferase (Hprt) locus...
  17. X CHROMOSOME REPLICATION
    ALAN CHINAULT; Fiscal Year: 1993
    ..transcription initiation sequences within a large region of the human X chromosome spanning the hypoxanthine phosphoribosyltransferase (HPRT) locus...
  18. NEUTRON DOSE PROTRACTION EFFECT ON TRANSFORMATION
    Colin Hill; Fiscal Year: 1992
    ....
  19. MUTANTS AND ALTERED RADIORESPONSE TO CELLS AND TUMORS
    Helen Evans; Fiscal Year: 1993
    ..Further, the results should reveal factors which affect the dose-response relationships and yield information as to the molecular mechanisms involved in radiation-induced damage leading to lethality, mutation, and oncogenesis...
  20. ACTIVATION OF CARCINOGENS BY UROTHELIUM IN VITRO
    Santhanam Swaminathan; Fiscal Year: 1991
    ..The information gained from these studies will be useful in identifying the key metabolic factors that might be involved in susceptibility to arylamine-induced bladder carcinogenesis...
  21. DEVELOPMENT OF A HUMAN SOMATIC GENE MUTAGENICITY ASSAY
    Edward Yurkow; Fiscal Year: 2000
    ..Since the proposed assay will satisfy an existing demand in the contract-testing industry for a test to detect specific types of human mutagens, the assay has tremendous commercial value. ..
  22. MUTAGENICITY OF ARSENIC IN MAMMALIAN CELLS
    TOM HEI; Fiscal Year: 2000
    ..By using specific DNA probes of other genes that have been regionally mapped to various sites on chromosome 11, the molecular mechanisms of mutation in A/L cells will also be examined. ..
  23. MODULATION OF DNA REPAIR BY P53 IN HUMAN UROEPITHELIUM
    Santhanam Swaminathan; Fiscal Year: 2001
    ..The results of these studies have important etiologic, mechanistic and therapeutic implications in human cancers. ..
  24. Uptake and Mutagenicity of Moderately Soluble Hexavalent Chromium
    DIANE STEARNS; Fiscal Year: 2008
    ..Understanding the mode of action of these chromates will provide a foundation for human risk assessment. [unreadable] [unreadable] [unreadable]..
  25. Comprehensive NAU/AZCC Cancer Research Partnership
    DIANE STEARNS; Fiscal Year: 2008
    ..Research activities include basic science, cancer education, and community outreach components. We propose 6 pilot projects, 4 full projects, and recruitment of 2 new faculty over the project lifetime. ..
  26. Transcriptional Control of Early Coronary Vascular Development
    RAVINDRA P MISRA; Fiscal Year: 2010
    ....
  27. GENETIC ANALYSIS OF PURINE METABOLISM IN LEISHMANIA DONO
    Buddy Ullman; Fiscal Year: 2007
    ..coli that overexpress hgprt genes, and[unreadable] intact parasites. ..
  28. R13 travel grant for Polyamine/parasite conference in Portland, OR
    Buddy Ullman; Fiscal Year: 2006
    ..abstract_text> ..
  29. Nucleoside Transporters of Plasmodium falciparum
    Buddy Ullman; Fiscal Year: 2007
    ..falciparum in order to test whether PfNT1 function is essential to the intact parasite. We will then characterize the resultant transport and growth phenotypes. ..
  30. THE ROLE OF SRF IN CARDIAC FUNCTION AND DEVELOPMENT
    RAVINDRA MISRA; Fiscal Year: 2005
    ..These studies will both elucidate the mechanisms by which SRF functions in heart and will establish powerful new methodologies for studying heart formation and function. ..
  31. MECHANISM-BASED DRUG SELECTION AND DESIGN: NUCLEOTIDE SA
    Buddy Ullman; Fiscal Year: 2003
    ..Concurrent experiments will determine how NTPase functions in AK HGXPRT-, and AT parasites, identify the protein(s) which regulate NTPase enzymatic activity, and evaluate the impact of abrogating NTPase expression on parasite viability. ..
  32. Polyamine Metabolism in Leishmania
    Buddy Ullman; Fiscal Year: 2008
    ..donovani. We propose, therefore, to ascertain whether the disparity in the abilities of ?lmarg L. mexicana and ?ldodc L. donovani to infect mice can be ascribed to species or gene differences. ..
  33. CHROMIUM(III) GENOTOXICITY--DIRECT AND INDIRECT PATHWAYS
    DIANE STEARNS; Fiscal Year: 2002
    ....
  34. Transformation of Human Endometrial Epithelial Cells
    David Kaufman; Fiscal Year: 2005
    ..abstract_text> ..
  35. Embryonic Stem Cell Model of Polyglutamine Disease
    MATTHEW LORINCZ; Fiscal Year: 2007
    ..Once the pathologic mechanisms of mutant huntingtin are understood it will become possible to design rational therapeutics. ..
  36. GENETIC DISSECTION OF TOXOPLASMA GONDII
    David Roos; Fiscal Year: 2008
    ..In addition to their value for the analysis of folate metabolism and drug resistance, these tools should be broadly applicable to other studies on the biology and biochemistry of Toxoplasma. ..
  37. GENOMIC IMPRINTING AND THE CLONING OF MICE
    Rudolf Jaenisch; Fiscal Year: 2008
    ..This program attempts to define the biological parameters which limit the nuclear cloning approach. ..
  38. Noncell autonomous control of Beta islet cells
    James DeGregori; Fiscal Year: 2004
    ..2) Further characterization of non-cell autonomous control of beta islet maintenance using islet transplantation. 3) Analysis of beta islet mass and function in mutant mice with defined hematopoietic defects. ..
  39. GENETIC ANALYSIS OF NUCLEOTIDE EXCISION REPAIR
    LAWRENCE THOMPSON; Fiscal Year: 2002
    ..These mechanistic insights will guide future structural studies on ERCC2. ..
  40. BIOMARKERS OF GENETIC DAMAGE AND ANTIOXIDANT
    Frederica Perera; Fiscal Year: 2001
    ..Once validated in this model population, these biomarkers would also have applicability in evaluating interventions in occupational cohorts and other populations highly exposed to carcinogens. ..
  41. Epigenetics, Stem Cells, and Cancer
    Rudolf Jaenisch; Fiscal Year: 2010
    ..Aim 3 will use nuclear transplantation as a criterion to define the genetic and epigenetic alterations of the cancer cell genome that interfere with reversion to pluripotency. ..
  42. ADDUCTS AS QUANTITATIVE MARKERS OF BUTADIENE MUTAGENESIS
    James Swenberg; Fiscal Year: 2009
    ..Ultimately these data will improve our understanding of critical mechanisms of toxicity and ability to accurately assess the risk of BD to humans. ..
  43. Imaging Dopamine Mediated Neurovascular Coupling
    Bruce Jenkins; Fiscal Year: 2010
    ..Finally, we will improve both our quantitative ability to acquire the data using higher contrast to noise techniques as well as model the signal changes using dopaminergic release and reuptake curves. ..
  44. GENE TARGETING STRATEGIES FOR THE TREATMENT OF OSTEOGENESIS IMPERFECTA
    David W Russell; Fiscal Year: 2010
    ..The research will also have broader implications, since gene targeting methods for human MSCs could potentially be applied to many diseases of bone, cartilage, muscle, and possibly other tissues. ..
  45. Novel approach to measure DNA adducts in humans
    ROBERT TURESKY; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  46. EARLY S PHASE REPLICATION SITES AS ENVIRONMENTAL TARGETS
    David Kaufman; Fiscal Year: 2002
    ....
  47. CONFOCAL LASER SCANNING MICROSCOPE
    David Kaufman; Fiscal Year: 2003
    ..Substantial preliminary and published data have been added to project descriptions. ..
  48. LC-MS/MS FOR HIGHLY SENSITIVE BIOMARKER DETECTION
    James Swenberg; Fiscal Year: 2005
    ..abstract_text> ..
  49. Enzyme Repair of Excoyclic Adducts
    Bo Hang; Fiscal Year: 2005
    ..abstract_text> ..
  50. VULNERABILITY OF THE FETUS/INFANT TO PAH, PM2.5 AND ETS.
    Frederica Perera; Fiscal Year: 2004
    ....
  51. HUMAN SENSITIVITY TO GENOTOXIC EFFECTS OF BUTADIENE
    Jonathan Ward; Fiscal Year: 2005
    ..how genetic variation in mEH influences human sensitivity to the genotoxic effects of BD, and better understand the role of variants in biotransformation genes in modifying human susceptibility to toxic chemicals ..
  52. 9th International Conference on Environmental Mutagens: Student Travel Expenses
    Jonathan Ward; Fiscal Year: 2005
    ..Awards will be made without regard to gender, race, ethnicity, nationality, or disability. ..
  53. Estrogens, Paracrine Factors, and Endometrial Cancer
    David Kaufman; Fiscal Year: 2006
    ..This study will test whether the hypothesized mechanism explains the differing responses of endometrium to estrogens and may allow development of a better assay of effects of SERMs and phytoestrogens on endometrium. ..
  54. Aromatase Inhibitor in Males with Adrenal Hyperplasia
    Kyriakie Sarafoglou; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  55. Combined MRI/PET Imager for Simultaneous Acquisition of PET/MRI Data
    Bruce Jenkins; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  56. BIOLOGY AND CONTROL OF LYME DISEASE BORRELIA
    Alan Barbour; Fiscal Year: 2004
    ..burgdorferi, its transmission, and reservoir host immunize responses. The results may also have relevance for the control of other vector-bone zoonotic diseases and perhaps for development of novel methods for vaccine delivery. ..
  57. Regulation of the Lymphocytic cell cycle by E2F
    James DeGregori; Fiscal Year: 2007
    ..Understanding the cellular functions of E2F1/2 and their target genes should facilitate a better understanding of organismal roles for these E2Fs at a more mechanistic level. ..
  58. Genotoxicity & Emergence of Genome Instability in Humans
    BARRY FINETTE; Fiscal Year: 2007
    ....
  59. Protein-protein interaction domains: targets for neuropharmacologic intervention
    KEVIN CALDWELL; Fiscal Year: 2007
    ..Thus, these studies will have significant impact on several research fields, including neurobiology, cell biology, biochemistry, and cancer biology. [unreadable] [unreadable]..