Background
The tail suspension test (TST) is a mouse screening test for antidepressants.
Methods
An F2 intercross was derived from NMRI and 129S6 inbred strains (n = 747). Mice underwent
standardized TST with 2 sessions: (1) baseline and (2) imipramine (30 mg/kg, intraperitoneally)
TST.
Results
A whole genome scan of this intercross mapped significant basal TST quantitative trait
loci (QTL) on chromosomes (chr) 5 (peak 61 cM, Lod 5.7), 12 (peak 43 cM, Lod 5.2),
and 18 (peak 51 cM, Lod 3.0). A suggestive QTL on chr 4 (peak 62 cM; Lod 3.1) overlapped
regions containing previously mapped QTLs. For TST imipramine response, QTL were mapped
on chr 1, 4, and 5. The chromosome 5 locus affected basal TST, antidepressant immobility
response, and tail suspension-induced hyperthermia (TSIH) behaviors. An outbred NMRI
F2 population provided further evidence for a chr 5 QTL. This chr 5 region harbors
a cluster of gamma aminobutyric acid (GABA)-A receptor subunits and the human syntenic
region includes chr 4p, 1p11, 12q24, and 22q11.24. A significant TSIH QTL (Tsih1)
mapped on chr 4 near the Leptin receptor (Lepr).
Conclusions
These QTL provide potential regions of interest for human genetic studies in stress-diathesis
models of psychiatric illness and antidepressant responsiveness.
Key Words
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Article info
Publication history
Published online: November 26, 2006
Accepted:
August 19,
2006
Received in revised form:
August 17,
2006
Received:
June 14,
2006
Identification
Copyright
© 2007 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
