Basal ganglia dopamine loss due to defect in purine recycling.
Several rare inherited disorders have provided valuable experiments of nature highlighting specific biological processes of particular importance to the survival or function of midbrain dopamine neurons. In both humans and mice, deficiency of hypoxanthine-guanine phosphoribosyl transferase (HPRT) is associated with profound loss of striatal dopamine, with relative preservation of other neurotransmitters. In the current studies of knockout mice, no morphological signs of abnormal development or degeneration were found in an exhaustive battery that included stereological and morphometric measures of midbrain dopamine neurons, electron microscopic studies of striatal axons and terminals, and stains for degeneration or gliosis. A novel culture model involving HPRT-deficient dopaminergic neurons also exhibited significant loss of dopamine without a morphological correlate. These results suggest that dopamine loss in HPRT deficiency has a biochemical rather than anatomical basis and imply that purine recycling to be a biochemical process of particular importance to the function of dopaminergic neurons.
Egami
Kiyoshi
K
Department of Neurology, Meyer Room 6-181, 600 North Wolfe Street, Johns Hopkins Hospital, Baltimore, MD 21287, USA.
Yitta
Silaja
S
Kasim
Suhail
S
Lewers
J Chris
JC
Roberts
Rosalinda C
RC
Lehar
Mohamed
M
Jinnah
H A
HA
D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005260:Female; D005911:Gliosis / Q000378:metabolism / Q000473:pathology; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism*; D009434:Neural Pathways / Q000378:metabolism / Q000473:pathology; D017729:Presynaptic Terminals / Q000378:metabolism / Q000473:pathology; D011687:Purines / Q000378:metabolism*; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism
D050483:Dopamine Plasma Membrane Transport Proteins; D011687:Purines; C493453:Slc18a2 protein, mouse; D050493:Vesicular Monoamine Transport Proteins; D007041:Hypoxanthine Phosphoribosyltransferase; D004298:Dopamine