Genetic dissection of the tail suspension test: A mouse model of stress vulnerability and antidepressant response
Genetic dissection of the tail suspension test: A mouse model of stress vulnerability and antidepressant response
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DOI：
10.1016/j.biopsych.2006.08.017
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发表时间：
2007-07-01
影响因子：
10.6
通讯作者：
Gershenfeld, Howard K.
中科院分区：
文献类型：
--
作者：
Liu, Xiaoqing;Stancliffe, Devin;Gershenfeld, Howard K.
背景资料：悬尾试验（TST）是一种筛选抗抑郁药物的试验。方法：用NMRI和129 S6近交系杂交获得F2代小鼠（n = 747）。结果：该杂交组合的全基因组扫描定位了显著的基础TST数量性状位点（QTL），分别位于第5、12、18号染色体（chr）上，峰值分别为61 cM、51 cM、5.7、43 cM、5.2和3.0。一个暗示性的QTL对chr 4（峰值62 cM; Lod 3.1）重叠区域含有以前映射的QTL。对于TST丙咪嗪反应，QTL定位在chr 1、4和5上。5号染色体位点影响基础TST，抗抑郁剂不动反应和尾部悬吊诱导的高热（TSIH）行为。远交NMRI F2群体提供了chr 5 QTL的进一步证据。该chr 5区域含有一簇γ-氨基丁酸（GABA）-A受体亚基，人类同线区域包括chr 4p、1 p11、12 q24和22q11.24。一个显著的TSIH QTL（Tsih 1）定位在chr 4上Lepr receptor（Lepr）附近。结论：这些QTL为精神疾病和抗抑郁反应的应激素质模型的人类遗传研究提供了潜在的感兴趣区域。
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, imitraperitoneally) 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.