α-Synuclein maps to a quantitative trait locus for alcohol preference and is differentially expressed in alcohol-preferring and -nonpreferring rats
| Autor: | Julie A. Ellison, Ting-Kai Li, Tiebing Liang, Lawrence Lumeng, Tatiana Foroud, Hwai Wen Chang, Lixiang Liu, Lucinda G. Carr, John P. Spence, Wendy N. Strother |
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| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
Untranslated region
Male DNA Complementary Alcohol Drinking Quantitative Trait Loci Synucleins Gene Expression Single-nucleotide polymorphism Nerve Tissue Proteins In situ hybridization Biology Quantitative trait locus Transfection Hippocampus Polymorphism Single Nucleotide Cell Line Complementary DNA Gene expression Animals Humans RNA Messenger Gene 3' Untranslated Regions Multidisciplinary Base Sequence Chromosome Mapping Rats Inbred Strains Biological Sciences Molecular biology Recombinant Proteins Rats Chromosome 4 alpha-Synuclein |
| Popis: | Total gene expression analysis (TOGA) was used to identify genes that are differentially expressed in brain regions between the alcohol-naïve, inbred alcohol-preferring (iP), and -nonpreferring (iNP) rats. α-Synuclein, expressed at >2-fold higher levels in the hippocampus of the iP than the iNP rat, was prioritized for further study. In situ hybridization was used to determine specific brain regions and cells expressing α-synuclein in the iP and iNP rats. Similar to α-synuclein mRNA levels, protein levels in the hippocampus were higher in iP rats than iNP rats. Higher protein levels were also observed in the caudate putamen of iP rats compared with iNP rats. Sequence analysis identified two single nucleotide polymorphisms in the 3′ UTR of the cDNA. The polymorphism was used to map the gene, by using recombination-based methods, to chromosome 4, within a quantitative trait locus for alcohol consumption that was identified in the iP and iNP rats. A nucleotide exchange in the iNP 3′ UTR reduced expression of the luciferase reporter gene in SK-N-SH neuroblastoma cells. These results suggest that differential expression of the α-synuclein gene may contribute to alcohol preference in the iP rats. |
| Databáze: | OpenAIRE |
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