223. Proteomic Analysis of the Striatum of Wild Type and HPRT-Deficient Mouse

Abstract

The enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) catalyzes the conversion of hypoxanthine and guanine to ionosine monophosphate and guanosine monophosphate in the purine salvage pathway. Mutations in HPRT gene cause Lesch-Nyhan disease (LND) in human, a central nervous system (CNS) disorder characterized by hyperuricemia, mental retardation, a severe movement disorder and compulsive self-mutilatory behavior. On a molecular level, LND is characterized by severe deficiency of the neurotransmitter dopamine in the basal ganglia. The HPRT-deficient mouse also displays a marked reduction in basal ganglia dopamine levels, making this animal a useful biochemical and molecular model for LND. In this study, we have used a combined two-dimensional electrophoresis/mass spectrometry proteomics approach to characterize the proteome of the striatum of wild type and HPRT-deficient C57B6 mice at the ages of 1 month, 2 months, 18 months and 24 months. Protein images were analyzed qualitatively and quantitatively with BioRad PDQuest software, and we have identified a small number of reproducible qualitative differences in the proteomes of wild type and HPRT-deficient mouse striata. These results represent the first global analysis of the gene expression and proteomic profiles in the mouse knockout model of this puzzling CNS disorder and model for CNS gene therapy.