title: Role of neuronal nitric oxide in the dopamine deficit of HPRT-deficient mice.
abstract: 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.
authors.affiliation: Center for Molecular Genetics, Department of Pediatrics, University of California, San Diego, CA, USA. douglas.smith@newcastle.edu.au
authors.forename: Doug W
authors.initials: DW
authors.lastname: Smith
authors.forename: Hyder A
authors.initials: HA
authors.lastname: Jinnah
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D004298:Dopamine / Q000172:deficiency* / Q000378:metabolism; D005260:Female; D006719:Homovanillic Acid / Q000378:metabolism; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics* / Q000378:metabolism; D007926:Lesch-Nyhan Syndrome / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000235:genetics* / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology
chemical_list: D015102:3,4-Dihydroxyphenylacetic Acid; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D007041:Hypoxanthine Phosphoribosyltransferase; D004298:Dopamine; D006719:Homovanillic Acid