Elevated UTP and CTP content in cultured neurons from HPRT-deficient transgenic mice

Sara Brosh, Pnina Boer, Oded Sperling, Esther Zoref-Shani*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Hypoxanthine-guanine phosphoribosyltransferase (EC 2.4.2.8.; HPRT) catalyzes the salvage synthesis of inosine-5'-monophosphate (IMP) and guanosine-5'-monophosphate (GMP) from the purine bases hypoxanthine and guanine, respectively. Complete deficiency of HPRT activity is associated with the Lesch-Nyhan syndrome (LNS), characterized by excessive purine production and severe neurological manifestations. The etiology of the metabolic consequences of HPRT deficiency is clarified, but that of the neurological manifestations is not yet understood. HPRT-deficient mice represent an experimental animal model of LNS. In search for a possible metabolic abnormality in LNS brains, connecting the neurological deficit to HPRT deficiency, the purine and pyrimidine nucleotide content of cultured neurons, prepared from HPRT-deficient transgenic mice, was now determined. The HPRT-deficient neuronal cultures exhibited a significantly elevated content of the pyrimidine nucleotides UTP (1.33-fold the normal level, p = 0.0002) and CTP (1.28-fold the normal level, p = 0.02), but normal content of the purine nucleotides ATP and GTP. This abnormality in neuronal pyrimidine nucleotide content may be associated with the pathophysiology of the neurological deficit in LNS.

Original languageEnglish
Pages (from-to)87-91
Number of pages5
JournalJournal of Molecular Neuroscience
Volume14
Issue number1-2
DOIs
StatePublished - 2000

Keywords

  • HPRT-deficient transgenic mice
  • Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency
  • Lesch-Nyhan syndrome (LNS)
  • Neuronal cultures
  • Purine nucleotides
  • Pyrimidine nucleotides

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