A comparison of striatal-dependent behaviors in wild-type and hemizygous Drd1a and Drd2 BAC transgenic mice.
A comparison of striatal-dependent behaviors in wild-type and hemizygous Drd1a and Drd2 BAC transgenic mice.
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DOI：
10.1523/jneurosci.0224-12.2012
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发表时间：
2012-07-04
期刊：
影响因子：
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通讯作者：
Kreitzer AC
中科院分区：
文献类型：
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作者：
Nelson AB;Hang GB;Grueter BA;Pascoli V;Luscher C;Malenka RC;Kreitzer AC
纹状体生理学和运动控制的研究越来越依赖于使用细菌人工染色体（BAC）转基因小鼠，所述转基因小鼠在多巴胺D1受体（D1 R）或多巴胺D2受体（D2 R）的遗传调控元件的控制下表达荧光团或其他基因。最近的三项研究比较了野生型、D1 R和D2 R BAC转基因小鼠，发现它们在生理和行为上存在显著差异，这对这些小鼠在正常回路功能研究中的应用提出了质疑。我们在野生型C57 BL/6小鼠和与C57 BL/6背景回交的半合子Drd 1a-tdomato（D1-Tmt）、Drd 1a-eGFP（D1-GFP）和Drd 2-eGFP（D2-GFP）小鼠中重复了这些研究的行为部分。我们的三个实验室独立地发现，在这四个小鼠系中，旷场运动、对可卡因（20 mg/kg）的急性运动反应、对每天注射可卡因（15 mg/kg）或安非他明（3 mg/kg）五天的运动敏化、可卡因（20 mg/kg）条件性位置偏爱以及对成对光和足电击的主动回避学习是不可区分的。这些结果表明，虽然筛选新的转基因小鼠品系的异常行为和生理是至关重要的，这些BAC转基因小鼠品系仍然是非常有价值的工具，用于评估纹状体运动控制和联想学习的细胞，突触和电路基础。
Studies of striatal physiology and motor control have increasingly relied on the use of bacterial artificial chromosome (BAC) transgenic mice expressing fluorophores or other genes under the control of genetic regulatory elements for the dopamine D1 receptor (D1R) or dopamine D2 receptor (D2R). Three recent studies have compared wild-type, D1R and D2R BAC transgenic mice, and found significant differences in physiology and behavior, calling into question the use of these mice in studies of normal circuit function. We repeated the behavioral portions of these studies in wild-type C57BL/6 mice and hemizygous Drd1a-tdomato (D1-Tmt), Drd1a-eGFP (D1-GFP), and Drd2-eGFP (D2-GFP) mice backcrossed into the C57BL/6 background. Our three laboratories independently found that open-field locomotion, acute locomotor responses to cocaine (20 mg/kg), locomotor sensitization to five days of daily injections of cocaine (15 mg/kg) or amphetamine (3 mg/kg), cocaine (20 mg/kg) conditioned place preference, and active avoidance learning to paired light and footshock were indistinguishable in these four mouse lines. These results suggest that while it is crucial to screen new transgenic mouse lines for abnormal behavior and physiology, these BAC transgenic mouse lines remain extremely valuable tools for evaluating the cellular, synaptic, and circuit basis of striatal motor control and associative learning.