Genetic dissection of the tail suspension test: a mouse model of stress vulnerability and antidepressant response.
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.
Liu
Xiaoqing
X
Department of Psychiatry, University of Texas Health Science Center at Houston, Houston, Texas, USA.
Stancliffe
Devin
D
Lee
Samuel
S
Mathur
Shelly
S
Gershenfeld
Howard K
HK
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002874:Chromosome Mapping; D033481:Chromosomes, Mammalian / Q000235:genetics; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005334:Fever / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D019417:Hindlimb Suspension / Q000502:physiology*; D007099:Imipramine / Q000494:pharmacology / Q000627:therapeutic use; D007103:Immobilization / Q000502:physiology / Q000523:psychology; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D008126:Lod Score; D051379:Mice; D008815:Mice, Inbred Strains; D040641:Quantitative Trait Loci / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics; D011963:Receptors, GABA-A / Q000187:drug effects / Q000235:genetics; D054411:Receptors, Leptin; D013315:Stress, Psychological / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics*; D009626:Terminology as Topic
D000928:Antidepressive Agents; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D054411:Receptors, Leptin; D007099:Imipramine