alpha-Synuclein maps to a quantitative trait locus for alcohol preference and is differentially expressed in alcohol-preferring and -nonpreferring rats.
Total gene expression analysis (TOGA) was used to identify genes that are differentially expressed in brain regions between the alcohol-naive, inbred alcohol-preferring (iP), and -nonpreferring (iNP) rats. alpha-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 alpha-synuclein in the iP and iNP rats. Similar to alpha-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 alpha-synuclein gene may contribute to alcohol preference in the iP rats.
Pubmed ID: 12665621
- Liang T
- Spence J
- Liu L
- Strother WN
- Chang HW
- Ellison JA
- Lumeng L
- Li TK
- Foroud T
- Carr LG
Proceedings of the National Academy of Sciences of the United States of America
April 15, 2003
- Agency: NIAAA NIH HHS, Id: AA00285
- Agency: NIAAA NIH HHS, Id: AA07611
- Agency: NIAAA NIH HHS, Id: AA10707
- Agency: NIAAA NIH HHS, Id: P60 AA007611
- Agency: NIAAA NIH HHS, Id: R01 AA010707
- 3' Untranslated Regions
- Alcohol Drinking
- Base Sequence
- Cell Line
- Chromosome Mapping
- DNA, Complementary
- Gene Expression
- Nerve Tissue Proteins
- Polymorphism, Single Nucleotide
- Quantitative Trait Loci
- RNA, Messenger
- Rats, Inbred Strains
- Recombinant Proteins
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