α-Synuclein maps to a quantitative trait locus for alcohol preference and is differentially expressed in alcohol-preferring and -nonpreferring rats

Tiebing Liang, John Spence, Lixiang Liu, Wendy N. Strother, Hwai Wen Chang, Julie A. Ellison, Lawrence Lumeng, Ting Kai Li, Tatiana Foroud, Lucinda G. Carr

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Abstract

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. 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.

Original languageEnglish
Pages (from-to)4690-4695
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number8
DOIs
StatePublished - Apr 15 2003

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Synucleins
Quantitative Trait Loci
Alcohols
3' Untranslated Regions
Hippocampus
Gene Expression
Chromosomes, Human, Pair 4
Putamen
Brain
Luciferases
Neuroblastoma
Reporter Genes
Alcohol Drinking
Genetic Recombination
Genes
In Situ Hybridization
Single Nucleotide Polymorphism
Sequence Analysis
Proteins
Nucleotides

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

α-Synuclein maps to a quantitative trait locus for alcohol preference and is differentially expressed in alcohol-preferring and -nonpreferring rats. / Liang, Tiebing; Spence, John; Liu, Lixiang; Strother, Wendy N.; Chang, Hwai Wen; Ellison, Julie A.; Lumeng, Lawrence; Li, Ting Kai; Foroud, Tatiana; Carr, Lucinda G.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 100, No. 8, 15.04.2003, p. 4690-4695.

Research output: Contribution to journalArticle

Liang, Tiebing ; Spence, John ; Liu, Lixiang ; Strother, Wendy N. ; Chang, Hwai Wen ; Ellison, Julie A. ; Lumeng, Lawrence ; Li, Ting Kai ; Foroud, Tatiana ; Carr, Lucinda G. / α-Synuclein maps to a quantitative trait locus for alcohol preference and is differentially expressed in alcohol-preferring and -nonpreferring rats. In: Proceedings of the National Academy of Sciences of the United States of America. 2003 ; Vol. 100, No. 8. pp. 4690-4695.
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abstract = "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. 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.",
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