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Related Experiment Videos

Expression profiling identifies novel candidate genes for ethanol sensitivity QTLs.

Erik J MacLaren1, Beth Bennett, Thomas E Johnson

  • 1Department of Pharmacology, University of Colorado at Denver and Health Sciences Center, Aurora, Colorado 80045, USA.

Mammalian Genome : Official Journal of the International Mammalian Genome Society
|February 9, 2006
PubMed
Summary

Genetic differences in mouse ethanol sensitivity were explored by examining gene expression in the cerebellum. Researchers identified novel candidate genes, including Slc22a4, Rassf2, and Tax1bp3, potentially influencing ethanol response duration.

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Area of Science:

  • Neurogenetics
  • Pharmacogenetics
  • Animal Models

Background:

  • Significant differences exist in ethanol-induced loss of righting response (LORR) duration between Inbred Long Sleep (ILS) and Inbred Short Sleep (ISS) mouse strains.
  • Quantitative trait loci (QTLs) associated with ethanol sensitivity have been identified, suggesting underlying genetic variations.

Purpose of the Study:

  • To identify candidate genes, particularly those with regulatory region differences, contributing to ethanol sensitivity.
  • To investigate genetic polymorphisms in promoter regions of differentially expressed genes within QTLs.

Main Methods:

  • Genome-wide expression profiling in cerebellum of ILS and ISS mice.
  • Direct sequencing of promoter regions for candidate genes identified through expression profiling.

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  • Analysis of transcription factor binding sites in identified polymorphisms.

    • Main Results:

    • Fifteen differentially expressed genes were identified within QTL regions.
    • Polymorphisms were found in the promoter regions of four genes, with three (Slc22a4, Rassf2, Tax1bp3) disrupting transcription factor binding sites.
    • Human orthologs of Slc22a4 and Xrcc5 are located in genomic regions linked to human ethanol sensitivity.

    Conclusions:

    • Novel candidate genes, including Slc22a4, Rassf2, and Tax1bp3, are implicated in the LORR phenotype.
    • These findings offer new targets for investigating the neurobiological mechanisms of ethanol sensitivity.
    • The study highlights the importance of regulatory regions in genetic contributions to ethanol sensitivity.