1. Mamm Genome. 2004 Aug;15(8):648-62.
Sex- and lineage-specific inheritance of depression-like behavior in the rat.
Solberg LC(1), Baum AE, Ahmadiyeh N, Shimomura K, Li R, Turek FW, Churchill GA,
Takahashi JS, Redei EE.
Author information:
(1)Department of Psychiatry and Behavioral Science, Northwestern University
Feinberg School of Medicine, 303 E. Chicago Avenue, Chicago, Illinois 60611, USA.
The Wistar-Kyoto (WKY) rat exhibits physiological and behavioral similarities to
endophenotypes of human depression. In the forced swim test (FST), a
well-characterized antidepressant-reversible test for behavioral despair in
rodents, WKYs express characteristics of behavioral despair; increased
immobility, and decreased climbing. To map genetic loci linked to behavior in the
FST, we conducted a quantitative trait loci (QTL) analysis of the segregating F2
generation of a WKY x Fisher 344 (F344) reciprocal intercross. Using
linear-model-based genome scans to include covariate (sex or lineage)-by-QTL
interaction effects, four significant QTL influencing climbing behavior were
identified. In addition, we identified three, seven, and two suggestive QTL for
climbing, immobility, and swimming, respectively. One of these loci was
pleiotropic, affecting both immobility and climbing. As found in human linkage
studies, several of these QTL showed sex- and/or lineage-dependent effects. A
simultaneous search strategy identified three epistatic locus pairs for climbing.
Multiple regression analysis was employed to characterize the joint contributions
of these QTL and to clarify the sex- and lineage-dependent effects. As expected
for complex traits, FST behavior is influenced by multiple QTL of small effect,
each contributing 5%-10%, accounting for a total 10%-30% of the phenotypic
variance. A number of loci mapped in this study share overlapping candidate
regions with previously identified emotionality QTL in mice as well as with
susceptibility loci recognized by linkage or genome scan analyses for major
depression or bipolar disorder in humans. The presence of these loci across
species suggests that these QTL may represent universal genetic factors
contributing to mood disorders.
PMCID: PMC3764448
PMID: 15457344 [PubMed - indexed for MEDLINE]
PUBMED: 15457344
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