Metabolic Brain Disease

, Volume 22, Issue 1, pp 39–43 | Cite as

Role of Neuronal Nitric Oxide in the Dopamine Deficit of HPRT-Deficient Mice

  • Doug W. SmithEmail author
  • Hyder A. Jinnah
original paper


Lesch-Nyhan disease is a debilitating disorder caused by a lack of purine salvage activity. Basal ganglia dopamine deficits manifest in both patients and hypoxanthine phosphoribosyltransferase (HPRT) mutant mice. We previously reported decreased activity in an oxidant sensitive enzyme in the brain of HPRT-deficient mice. In the present study, we have investigated whether one source of free radicals, neuronal nitric oxide synthase (NOS1), contributes to the dopamine deficit associated with HPRT deficiency. HPRT knockout and wild-type mice were bred, either to lack, or to have the full complement of NOS1 alleles. Double mutant mice had striatal dopamine and dopamine metabolite levels indistinguishable from the HPRT single mutant counterparts. These results indicate that NOS1 produced nitric oxide does not contribute to the dopamine deficit seen in HPRT deficiency.


Inborn error in metabolism Dopaminergic system dysfunction Oxidative stress Mitochondrial aconitase Nitric oxide 



This work was supported by funding from the Lesch-Nyhan Children’s Research Foundation and NIH (NS44544-0IAI).


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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.Center for Molecular Genetics, Department of PediatricsUniversity of CaliforniaSan DiegoUSA
  2. 2.Neurology DepartmentJohns Hopkins UniversityBaltimoreUSA
  3. 3.Discipline of Anatomy, School of Biomedical SciencesUniversity of NewcastleCallaghanAustralia

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