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Related Experiment Videos

Mapping quantitative trait loci mediating sensitivity to etomidate.

Chris Downing1, Elaine H Shen, Victoria J Simpson

  • 1Institute for Behavioral Genetics, University of Colorado, Campus Box 447, Boulder, Colorado 80309-0447, USA. cdowning@colorado.edu

Mammalian Genome : Official Journal of the International Mammalian Genome Society
|July 25, 2003
PubMed
Summary

Genetic mapping identified quantitative trait loci (QTLs) influencing anesthetic sensitivity in Long- and Short-Sleep mice. Differences in etomidate-induced loss of righting reflex (LORR) are likely due to central nervous system sensitivity, not metabolism.

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Area of Science:

  • Neurogenetics
  • Pharmacology
  • Animal Models

Background:

  • Long- and Short-Sleep (LS and SS) mice exhibit differential responses to ethanol-induced loss of righting reflex (LORR).
  • These mouse lines also show varied sensitivity to anesthetic agents, suggesting a genetic basis for anesthetic response.

Purpose of the Study:

  • To identify quantitative trait loci (QTLs) associated with the duration of etomidate-induced LORR.
  • To map QTLs influencing brain etomidate levels (BEL) after regaining the righting reflex.
  • To investigate the genetic underpinnings of differential anesthetic sensitivity in LS and SS mice.

Main Methods:

  • A two-stage genetic mapping strategy was employed using recombinant-inbred (RI) strains (LSXSS) and an F(2) intercross population (ILS x ISS).
  • Analysis involved assessing etomidate-induced LORR duration and BEL.

Related Experiment Videos

  • Quantitative trait loci (QTLs) were identified through linkage analysis on mouse chromosomes.

    • Main Results:

    • A significant QTL for etomidate-induced LORR was mapped to mouse Chromosome (Chr) 12 in the F(2) population.
    • Two significant QTLs for BEL were identified on Chrs 6 and 12 in the F(2) population.
    • Data suggested that observed differences in LORR were primarily due to variations in central nervous system sensitivity to etomidate, rather than altered metabolism.

    Conclusions:

    • Genetic factors on mouse Chr 12 significantly influence etomidate-induced LORR duration.
    • Genetic loci on Chrs 6 and 12 mediate brain etomidate levels.
    • The identification of overlapping QTL regions for etomidate and ethanol sensitivity suggests potential shared genetic mechanisms.