title: Bone marrow transplantation does not ameliorate the neurologic symptoms in mice deficient in hypoxanthine guanine phosphoribosyl transferase (HPRT).
abstract: The use of bone marrow transplantation (BMT) for the treatment of genetic diseases with neurologic involvement has yielded mixed results. We have employed a mouse model of Lesch-Nyhan disease (LND) to assess the efficacy of BMT in ameliorating the neurologic manifestations of the disease. Adult HPRT-deficient mice exhibit a measurable decrease in striatal dopamine levels and a hypersensitivity to amphetamine. Marrow-ablated adult HPRT-deficient mice were transplanted with marrow from congenic HPRT-expressing mice. BMT altered neither the neurochemical nor the behavioral phenotypes in either HPRT-positive or HPRT-deficient mice. Barring any important species differences, these results suggest that BMT in its present form may not be an effective therapy for Lesch-Nyhan syndrome.
authors.affiliation: Dept. of Pediatrics, UCSD School of Medicine, La Jolla, CA 92093, USA.
authors.forename: B E
authors.initials: BE
authors.lastname: Wojcik
authors.forename: H A
authors.initials: HA
authors.lastname: Jinnah
authors.forename: C E
authors.initials: CE
authors.lastname: Muller-Sieburg
authors.forename: T
authors.initials: T
authors.lastname: Friedmann
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D016026:Bone Marrow Transplantation; D003913:Dextroamphetamine / Q000494:pharmacology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D005260:Female; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency*; D007926:Lesch-Nyhan Syndrome / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology / Q000601:surgery; D051379:Mice; D008810:Mice, Inbred C57BL; D009422:Nervous System Diseases / Q000209:etiology*; D016548:Prosencephalon / Q000378:metabolism
chemical_list: D007041:Hypoxanthine Phosphoribosyltransferase; D003913:Dextroamphetamine; D004298:Dopamine