Genomic regions controlling corticosterone levels in rats

Biol Psychiatry. 2004 Mar 15;55(6):634-41. doi: 10.1016/j.biopsych.2003.11.005.

Abstract

Background: The identification of genetic factors controlling stress-responsiveness should advance the understanding of susceptibility to psychiatric illness.

Methods: Rat strains, F344/NHsd and LEW/NHsd, which differ in measures of stress-responsiveness and behaviors modeling psychiatric disorders, were bred to generate F2 progeny that were used in a quantitative trait loci (QTL) analysis to identify genomic regions influencing late-afternoon corticosterone levels.

Results: Regions on chromosomes 4 and 10 previously identified as influencing autoimmune phenomena were the most significant QTL observed, reaching suggestive significance at the genome-wide level. Congenic animals targeting these regions with F344/NHsd deoxyribonucleic acid on a DA/Bkl genomic background demonstrated corticosterone levels approximating those of F344/NHsd rats and differing significantly from DA/Bkl rats.

Conclusions: Specific genomic regions influence both corticosterone levels and stress-related disease susceptibility. These findings not only represent the first identification of QTL controlling corticosterone levels but also suggest a mechanism underlying genetic differences in stress-responsiveness.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Congenic
  • Chi-Square Distribution
  • Chromosome Mapping
  • Corticosterone / blood*
  • Corticosterone / genetics
  • Genetic Linkage
  • Genome*
  • Lod Score
  • Male
  • Molecular Biology / methods
  • Quantitative Trait Loci / physiology
  • Rats
  • Rats, Inbred F344
  • Rats, Inbred Lew
  • Stress Disorders, Traumatic / genetics
  • Stress Disorders, Traumatic / metabolism*

Substances

  • Corticosterone