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Related Experiment Videos

Alcohol and genetics: new models.

John C Crabbe1

  • 1Department of Behavioral Neuroscience, Portland Alcohol Research Center, Portland, Oregon 97201, USA. crabbe@ohsu.edu

American Journal of Medical Genetics
|November 29, 2002
PubMed
Summary
This summary is machine-generated.

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Genetic animal models reveal complex genetic influences on alcoholism. Research identifies specific genes linked to alcohol withdrawal severity, advancing understanding of addiction susceptibility.

Area of Science:

  • Neurogenetics
  • Behavioral Genetics
  • Addiction Research

Background:

  • Alcoholism is a complex genetic disorder influenced by multiple genes.
  • Genetic animal models are crucial for studying the mechanisms of alcohol's effects.
  • Previous research has modeled alcohol's rewarding effects, tolerance, brain consequences, and withdrawal.

Purpose of the Study:

  • To identify specific genes contributing to alcohol's effects and addiction susceptibility.
  • To understand the genetic basis of alcohol withdrawal severity.
  • To advance mechanistic studies of alcoholism through genetic approaches.

Main Methods:

  • Utilized classical genetic methods like inbred strain analysis and selectively bred lines.
  • Employed quantitative trait loci (QTL) mapping based on gene sequence polymorphisms.

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  • Conducted gene expression studies and candidate gene targeting, including null mutants.
  • Used multiple congenic strains to narrow down gene regions associated with withdrawal severity.

    • Main Results:

    • Mapped numerous quantitative trait loci (QTL) for genes influencing alcohol sensitivity, tolerance, reward, and withdrawal.
    • Significantly advanced gene mapping for a withdrawal QTL on mouse chromosome 4.
    • Isolated the gene for increased withdrawal severity to a small chromosomal region (<1 cM) with fewer than 20 genes.
    • Identified a strong candidate gene encoding a PDZ binding domain zinc finger protein.

    Conclusions:

    • Genetic factors significantly influence alcohol withdrawal severity and overall addiction susceptibility.
    • Precise identification of genes requires detailed phenotypic descriptions and consideration of gene interactions (epistasis) and genetic background.
    • Future progress depends on identifying more risk genes and understanding their complex interplay in the multi-behavioral syndrome of alcoholism.