Genomic regions controlling corticosterone levels in rats.
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.
Potenza
Marc N
MN
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06519, USA.
Brodkin
Edward S
ES
Joe
Bina
B
Luo
Xingguang
X
Remmers
Elaine F
EF
Wilder
Ronald L
RL
Nestler
Eric J
EJ
Gelernter
Joel
J
D000818:Animals; D020296:Animals, Congenic; D016009:Chi-Square Distribution; D002874:Chromosome Mapping; D003345:Corticosterone / Q000097:blood* / Q000235:genetics; D008040:Genetic Linkage; D016678:Genome; D008126:Lod Score; D008297:Male; D008967:Molecular Biology / Q000379:methods; D040641:Quantitative Trait Loci / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D040921:Stress Disorders, Traumatic / Q000235:genetics / Q000378:metabolism*
D003345:Corticosterone