title: A Golgi study of neuronal architecture in a genetic mouse model for Lesch-Nyhan disease.
abstract: Lesch-Nyhan disease (LND) is an inherited disorder associated with deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT), an enzyme essential for purine recycling. The clinical manifestations of the disorder and several neurochemical studies have pointed towards a defect in the striatum, but histological studies of autopsied brain specimens have not revealed any consistent abnormalities. An HPRT-deficient (HPRT-) mouse that has been produced as a model for the disease also exhibits neurochemical abnormalities of the striatum without obvious histological correlates. In the current studies, Golgi-Cox histochemistry was used to evaluate the fine structure of medium spiny I neurons from the striatum in the HPRT- mice. To determine if any abnormalities might be restricted to striatal neurons, the pyramidal projection neurons of layer 5 of the cerebral cortex were also evaluated. Neurons from both regions demonstrated a normal distribution, orientation, and gross morphology. There was no evidence for an abnormal developmental process or degeneration. However, both regions demonstrated a paucity of neurons with very long dendrites and a reduction in dendritic spines that depended upon the distance from the cell body. These findings demonstrate that HPRT deficiency is associated with changes in neuronal architecture in the HPRT- mice. Similar abnormalities in the LND brain could underlie some of the clinical manifestations.
authors.affiliation: Department of Neurology, Meyer Room 6-181, Johns Hopkins Hospital, Baltimore, MD 21287, USA.
authors.forename: Ivan
authors.initials: I
authors.lastname: Mikolaenko
authors.forename: Lekha M
authors.initials: LM
authors.lastname: Rao
authors.forename: Rosalinda C
authors.initials: RC
authors.lastname: Roberts
authors.forename: Bryan
authors.initials: B
authors.lastname: Kolb
authors.forename: H A
authors.initials: HA
authors.lastname: Jinnah
mesh_terms: D000818:Animals; D048430:Cell Shape / Q000235:genetics; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D049229:Dendritic Spines / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D005260:Female; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D019044:Image Cytometry; D007926:Lesch-Nyhan Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D009474:Neurons / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D016622:Silver Staining
chemical_list: D007041:Hypoxanthine Phosphoribosyltransferase