title: Monoamine deficiency in a transgenic (Hprt-) mouse model of Lesch-Nyhan syndrome.
abstract: The integrity of forebrain monoamine systems has been assessed both biochemically and immunohistochemically in transgenic mice carrying the mutant hprt-bm2 gene, an animal model of Lesch-Nyhan syndrome. The mutant mice manifested 20-30% depletions of forebrain dopamine, and corresponding increases in dopamine turnover. By contrast, the mutant mice manifested normal tyrosine hydroxylase immunostaining of catecholamine cell bodies and terminals throughout the forebrain, and cell counts revealed no detectable loss of ventral mesencephalic dopamine neurones. Serotonin concentrations were also depleted, whereas no significant changes were found in noradrenaline or adrenaline, methylhydroxyphenylglycol (MHPG) or 5-hydroxyindoleacetic acid. The results indicate that a primary genetic deficiency in purine salvage pathways is associated with additional changes in forebrain monoamine metabolism in mouse as in man, although these changes are less pronounced in the animal model than in the human syndrome. The biochemical changes were not associated with explicit degeneration of the associated populations of neurones.
authors.affiliation: Department of Experimental Psychology, University of Cambridge, U.K.
authors.forename: S B
authors.initials: SB
authors.lastname: Dunnett
authors.forename: D J
authors.initials: DJ
authors.lastname: Sirinathsinghji
authors.forename: R
authors.initials: R
authors.lastname: Heavens
authors.forename: D C
authors.initials: DC
authors.lastname: Rogers
authors.forename: M R
authors.initials: MR
authors.lastname: Kuehn
mesh_terms: D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D004195:Disease Models, Animal; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics* / Q000378:metabolism; D007926:Lesch-Nyhan Syndrome / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
chemical_list: D015306:Biogenic Monoamines; D014446:Tyrosine 3-Monooxygenase; D007041:Hypoxanthine Phosphoribosyltransferase