RGD Reference Report - Sex- and lineage-specific inheritance of depression-like behavior in the rat. - Rat Genome Database

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Sex- and lineage-specific inheritance of depression-like behavior in the rat.

Authors: Solberg, LC  Baum, AE  Ahmadiyeh, N  Shimomura, K  Li, R  Turek, FW  Churchill, GA  Takahashi, JS  Redei, EE 
Citation: Solberg LC, etal., Mamm Genome 2004 Aug;15(8):648-62.
RGD ID: 1302894
Pubmed: PMID:15457344   (View Abstract at PubMed)
PMCID: PMC3764448   (View Article at PubMed Central)
DOI: DOI:10.1007/s00335-004-2326-z   (Journal Full-text)

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.



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Mammalian Phenotype

Objects Annotated

QTLs
Despr1  (Despair related QTL 1)
Despr10  (Despair related QTL 10)
Despr11  (Despair related QTL 11)
Despr12  (Despair related QTL 12)
Despr13  (Despair related QTL 13)
Despr14  (Despair related QTL 14)
Despr15  (Despair related QTL 15)
Despr2  (Despair related QTL 2)
Despr3  (Despair related QTL3)
Despr4  (Despair related QTL 4)
Despr5  (Despair related QTL 5)
Despr6  (Despair related QTL 6)
Despr7  (Despair related QTL 7)
Despr8  (Despair related QTL 8)
Despr9  (Despair related QTL 9)

Strains
F344/NHsd  (F344/NHsd)
WKY/NHsd  (NA)


Additional Information