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首页> 外文期刊>Genes, brain, and behavior >A transgenic zebrafish model for monitoring glucocorticoid receptor activity
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A transgenic zebrafish model for monitoring glucocorticoid receptor activity

机译：用于监测糖皮质激素受体活性的转基因斑马鱼模型

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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 socioeconomically 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.
机译：由糖皮质激素受体和糖皮质激素反应元件相互作用产生的基因调控是应激反应信号转导的标志性特征。糖皮质激素产生和糖皮质激素受体活性的失衡与社会经济严重的神经精神疾病有关，因此，有必要建立体内模型来帮助理解疾病的进展和管理。因此，我们开发了具有六个糖皮质激素响应元件的转基因SR4G斑马鱼报告基因系，用于在糖皮质激素受体激活后促进短半衰期绿色荧光蛋白的表达。在此，我们记录了该报告基因系对慢性和急性外源性糖皮质激素治疗的反应能力。在包括脑在内的多种组织中，响应转基因激活的绿色荧光蛋白表达较高，并且在受影响的区域提供了单细胞分辨率。这些反应的特异性通过米非司酮的部分激动剂和糖皮质激素受体的突变来证明。重要的是，该报道分子还对内源性应激反应信号的时间动态进行了建模，包括高渗应激后糖皮质激素皮质醇的产生增加以及基础皮质醇浓度随昼夜节律的波动。综上所述，这些结果表征了我们新近开发的报道分子，用于阐明应激反应信号的环境或遗传修饰因子，可为了解神经精神疾病（例如重性抑郁症）的神经元机制提供见识。

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