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首页> 外文期刊>The European Journal of Neuroscience >Preserved dopaminergic homeostasis and dopamine-related behaviour in hemizygous TH-Cre mice
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Preserved dopaminergic homeostasis and dopamine-related behaviour in hemizygous TH-Cre mice

机译:在嗜血症Th-Cre小鼠中保存了多巴胺能稳态和多巴胺相关的行为

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摘要

Cre-driver mouse lines have been extensively used as genetic tools to target and manipulate genetically defined neuronal populations by expression of Cre recombinase under selected gene promoters. This approach has greatly advanced neuroscience but interpretations are hampered by the fact that most Cre-driver lines have not been thoroughly characterized. Thus, a phenotypic characterization is of major importance to reveal potential aberrant phenotypes prior to implementation and usage to selectively inactivate or induce transgene expression. Here, we present a biochemical and behavioural assessment of the dopaminergic system in hemizygous tyrosine hydroxylase (TH)-Cre mice in comparison to wild-type (WT) controls. Our data show that TH-Cre mice display preserved dopaminergic homeostasis with unaltered levels of TH and dopamine as well as unaffected dopamine turnover in striatum. TH-Cre mice also show preserved dopamine transporter expression and function supporting sustained dopaminergic transmission. In addition, TH-Cre mice demonstrate normal responses in basic behavioural paradigms related to dopaminergic signalling including locomotor activity, reward preference and anxiolytic behaviour. Our results suggest that TH-Cre mice represent a valid tool to study the dopamine system, though careful characterization must always be performed to prevent false interpretations following Cre-dependent transgene expression and manipulation of selected neuronal pathways.
机译:通过在所选基因启动子下表达CRE重组酶,Cre-Driver鼠标系已被广泛地用作遗传工具以靶向和操纵遗传定义的神经元群。这种方法具有极大的神经科学,但解释被大多数Cre-Driver系列没有完全表征。因此,表型表征是在实施和使用之前揭示潜在的异常表型以选择性地灭活或诱导转基因表达的主要重要性。在这里,与野生型(WT)对照相比,我们介绍了半腺苷酪氨酸羟化酶(TH)-Cre小鼠中的多巴胺能系统的生化和行为评估。我们的数据表明,Th-Cre小鼠展示保存的多巴胺能稳定性,卵黄和多巴胺水平,以及在纹状体中未受影响的多巴胺周转。 TH-CRE小鼠还显示保存的多巴胺转运蛋白表达和功能支持持续多巴胺能传输。此外,Th-Cre小鼠证明了与多巴胺能信号传导相关的基本行为范式的正常反应,包括运动活性,奖励偏好和抗焦虑行为。我们的研究结果表明,Th-Cre小鼠代表了研究多巴胺系统的有效工具,但必须始终进行仔细表征以防止依赖于CRE依赖性转基因表达后的虚假解释和所选择的神经元途径的操纵。

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