A transgenic zebrafish model for monitoring glucocorticoid receptor activity.
A transgenic zebrafish model for monitoring glucocorticoid receptor activity.
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DOI：
10.1111/gbb.12135
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发表时间：
2014-06
期刊：
影响因子：
--
通讯作者：
Clark KJ
中科院分区：
文献类型：
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作者：
Krug RG 2nd;Poshusta TL;Skuster KJ;Berg MR;Gardner SL;Clark KJ
糖皮质激素受体和糖皮质激素反应元件相互作用导致的基因调控是应激反应信号的一个显著特征。糖皮质激素产生和糖皮质激素受体活性失衡与社会经济致残性神经精神障碍有关，因此有必要开发体内模型来帮助了解疾病的进展和治疗。因此，我们建立了含有六个糖皮质激素反应元件的转基因斑马鱼报告系SR4G，用于促进糖皮质激素受体激活后一个半衰期较短的绿色荧光蛋白的表达。在此，我们记录了该报告系对慢性和急性外源性糖皮质激素治疗的反应能力。转基因激活后的绿色荧光蛋白在包括大脑在内的各种组织中都有很高的表达，并在受影响的区域提供了单细胞分辨率。使用部分激动剂米非司酮和糖皮质激素受体突变证明了这些反应的特异性。重要的是，报道线还模拟了内源性应激反应信号的时间动态，包括高渗应激后糖皮质激素产生的增加以及基础皮质醇浓度随昼夜节律的波动。综上所述，这些结果是我们新开发的用于阐明应激反应信号的环境或遗传修饰物的报道线的特征，这可能为揭示神经精神障碍(如严重抑郁障碍)的神经机制提供见解。
Gene regulation resulting from glucocorticoid receptor and glucocorticoid response element interactions is a hallmark feature of stress response signaling. Imbalanced glucocorticoid production and glucocorticoid receptor activity have been linked to socio-economically crippling neuropsychiatric disorders, and accordingly there is a need to develop in vivo models to help understand disease progression and management. Therefore, we developed the transgenic SR4G zebrafish reporter line with six glucocorticoid response elements used to promote expression of a short half-life green fluorescent protein following glucocorticoid receptor activation. Herein, we document the ability of this reporter line to respond to both chronic and acute exogenous glucocorticoid treatment. The green fluorescent protein expression in response to transgene activation was high in a variety of tissues including the brain, and provided single cell resolution in the effected regions. The specificity of these responses is demonstrated using the partial agonist mifepristone and mutation of the glucocorticoid receptor. Importantly, the reporter line also modeled the temporal dynamics of endogenous stress response signaling, including the increased production of the glucocorticoid cortisol following hyperosmotic stress and the fluctuations of basal cortisol concentrations with the circadian rhythm. Taken together, these results characterize our newly developed reporter line for elucidating environmental or genetic modifiers of stress response signaling, which may provide insights to the neuronal mechanisms underlying neuropsychiatric disorders such as major depressive disorder.
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影响因子：
9.8
作者：
Dickmeis T;Lahiri K;Nica G;Vallone D;Santoriello C;Neumann CJ;Hammerschmidt M;Foulkes NS
通讯作者：
Foulkes NS
影响因子：
3.7
作者：
Cachat J;Stewart A;Utterback E;Hart P;Gaikwad S;Wong K;Kyzar E;Wu N;Kalueff AV
通讯作者：
Kalueff AV
影响因子：
3.5
作者：
Hurd, MW;Cahill, GM
通讯作者：
Cahill, GM
DOI：
10.1073/pnas.1308335110
发表时间：
2013-08-20
影响因子：
11.1
作者：
Jao, Li-En;Wente, Susan R.;Chen, Wenbiao
通讯作者：
Chen, Wenbiao
影响因子：
46.9
作者：
通讯作者：
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