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Related Experiment Video

Updated: May 12, 2026

Paradigms for Pharmacological Characterization of C. elegans Synaptic Transmission Mutants
18:01

Paradigms for Pharmacological Characterization of C. elegans Synaptic Transmission Mutants

Published on: August 18, 2008

Differential network analysis reveals genetic effects on catalepsy modules.

Ovidiu D Iancu1, Denesa Oberbeck, Priscila Darakjian

  • 1Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, USA. iancuo@ohsu.edu

Plos One
|April 5, 2013
PubMed
Summary

Selective breeding successfully altered haloperidol-induced catalepsy in mice across diverse genetic backgrounds. Gene coexpression networks changed, highlighting subnetwork-level alterations rather than broad gene expression shifts.

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Area of Science:

  • Genetics
  • Neuroscience
  • Pharmacology

Background:

  • Selective breeding is a powerful tool for studying genetic contributions to complex traits.
  • Haloperidol-induced catalepsy is a well-established behavioral assay used to investigate antipsychotic drug mechanisms.
  • Understanding genetic architecture of drug response is crucial for personalized medicine.

Purpose of the Study:

  • To investigate the impact of selective breeding on haloperidol-induced catalepsy across different mouse genetic backgrounds.
  • To identify changes in gene coexpression networks associated with selective breeding for catalepsy.
  • To determine if genetic polymorphisms influence transcript connectivity without altering absolute expression levels.

Main Methods:

  • Bi-directional selective breeding for haloperidol-induced catalepsy.

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  • Utilizing three mouse populations: F2 intercross, heterogeneous stock (HS4), and heterogeneous stock-Collaborative Cross (HS-CC).
  • Employing a custom differential network analysis to assess gene coexpression patterns.

    • Main Results:

    • Successful selection for haloperidol response in all three genetic backgrounds within three generations.
    • Significant, concordant changes in gene coexpression patterns across genetic backgrounds.
    • Modest, non-concordant absolute gene expression changes despite similar phenotypic outcomes.
    • Identification of allelic content differences linked to transcript connectivity changes.

    Conclusions:

    • Selective breeding impacts gene coexpression at the subnetwork level, affecting modules rather than specific transcripts.
    • Genetic polymorphisms can alter transcript connectivity independently of absolute expression levels.
    • These findings provide insights into the genetic basis of drug response and behavioral traits.