Journal of Molecular Neuroscience

, Volume 14, Issue 1–2, pp 87–91 | Cite as

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

  • Sara Brosh
  • Pnina Boer
  • Oded Sperling
  • Esther Zoref-Shani


Hypoxanthine-guanine phosphoribosyltransferase (EC; 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.

Index Entries

Purine nucleotides pyrimidine nucleotides Lesch-Nyhan syndrome (LNS) Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency neuronal cultures HPRT-deficient transgenic mice 


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Copyright information

© Humana Press Inc 2000

Authors and Affiliations

  • Sara Brosh
    • 1
  • Pnina Boer
    • 1
  • Oded Sperling
    • 1
    • 2
    • 3
  • Esther Zoref-Shani
    • 3
  1. 1.Felsenstein Medical Research CenterRabin Medical CenterPetah-TikvaIsrael
  2. 2.Department of Clinical BiochemistryRabin Medical CenterPetah-TikvaIsrael
  3. 3.Department of Clinical Biochemistry, Sackler School of MedicineTel Aviv UniversityTel-AvivIsrael

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