Altered baseline and amphetamine-mediated behavioral profiles in dopamine transporter Cre (DAT-Ires-Cre) mice compared to tyrosine hydroxylase Cre (TH-Cre) mice.
Altered baseline and amphetamine-mediated behavioral profiles in dopamine transporter Cre (DAT-Ires-Cre) mice compared to tyrosine hydroxylase Cre (TH-Cre) mice.
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DOI：
10.1007/s00213-020-05635-4
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发表时间：
2020-12
影响因子：
3.4
通讯作者：
Veenstra-VanderWeele, Jeremy
中科院分区：
文献类型：
--
作者：
Chohan, Muhammad O.;Esses, Sari;Haft, Julia;Ahmari, Susanne;Veenstra-VanderWeele, Jeremy
关键词：
在多巴胺转运体（DAT）或酪氨酸羟化酶（TH）启动子的调控下表达cree -重组酶的转基因小鼠系通常用于研究多巴胺（DA）系统。虽然使用TH启动子似乎不太容易改变天然基因表达，但在DAT位点插入转基因会导致DAT表达和功能降低。在基因定向行为实验中，这种混淆有时会被忽视。我们试图评估DAT-Ires-Cre和TH-Cre转基因系在DA激动剂行为药理学实验中的适用性。我们假设DAT-Ires-Cre表达会影响dat介导的行为，但未观察到TH-Cre表达的影响。在混合129S6/C57BL/6和纯C57BL/6背景下饲养的da - ires - cre和TH-Cre小鼠，评估其新动性、基线性和安非他胺（AMPH）诱导的运动；以及AMPH和D1激动剂（SKF-38393）诱导的保存行为。在混合129S6/C57BL/6和纯C57BL/6背景下的dc - ires - cre小鼠均表现出新事物诱导的活性增加和amph诱导的运动减少，但amph诱导的刻板印象结果不一。两种背景下的TH-Cre小鼠均表现出典型的基线活动和amph诱导的刻板印象，仅在混合背景下观察到amph诱导的运动差异。两种转基因系均表现出未改变的SKF-38393诱导的梳理行为。我们的研究结果表明，DAT- ires - cre转基因系可能导致依赖于DAT表达的实验混淆。这里研究的TH-Cre转基因系可能是一个更有用的选择，这取决于背景菌株，因为它缺乏基线和药物诱导的表型。这些数据强调了在使用转基因小鼠的研究中适当控制的重要性。
Transgenic mouse lines expressing Cre-recombinase under the regulation of either dopamine transporter (DAT) or tyrosine hydroxylase (TH) promoters are commonly used to study the dopamine (DA) system. While use of the TH promoter appears to have less liability to changes in native gene expression, transgene insertion in the DAT locus results in reduced DAT expression and function. This confound is sometimes overlooked in genetically targeted behavioral experiments. We sought to evaluate the suitability of DAT-Ires-Cre and TH-Cre transgenic lines for behavioral pharmacology experiments with DA agonists. We hypothesized that DAT-Ires-Cre expression would impact DAT-mediated behaviors, but no impact of TH-Cre expression would be observed. DAT-Ires-Cre and TH-Cre mice bred on mixed 129S6/C57BL/6 and pure C57BL/6 backgrounds were evaluated for novelty-induced, baseline, and amphetamine (AMPH)-induced locomotion; and for AMPH and D1 agonist (SKF-38393)-induced preservative behaviors. DAT-Ires-Cre mice on both mixed 129S6/C57BL/6 and pure C57BL/6 backgrounds displayed increased novelty-induced activity and decreased AMPH-induced locomotion, with mixed results for AMPH-induced stereotypy. TH-Cre mice on both backgrounds showed typical baseline activity and AMPH-induced stereotypy, with a difference in AMPH-induced locomotion observed only on the mixed background. Both transgenic lines displayed unaltered SKF-38393 induced grooming behavior. Our findings indicate that the DAT-Ires-Cre transgenic line may lead to confounds for experiments that are dependent on DAT expression. The TH-Cre transgenic line studied here may be a more useful option, depending on background strain, because of its lack of baseline and drug-induced phenotypes. These data highlight the importance of appropriate controls in studies employing transgenic mice.
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神经元型特异性信号，用于腹侧对段区域的奖励和惩罚。
影响因子：
64.8
作者：
Cohen, Jeremiah Y.;Haesler, Sebastian;Vong, Linh;Lowell, Bradford B.;Uchida, Naoshige
通讯作者：
Uchida, Naoshige
影响因子：
5.3
作者：
Forni, Paolo E.;Scuoppo, Claudio;Ponzetto, Carola
通讯作者：
Ponzetto, Carola
DOI：
10.1016/0169-328x(93)90059-x
发表时间：
1993-12-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
AUGOOD, SJ;WESTMORE, K;EMSON, PC
通讯作者：
EMSON, PC
影响因子：
5.3
作者：
Chen, Edison;Lallai, Valeria;Fowler, Christie D.
通讯作者：
Fowler, Christie D.
影响因子：
5.3
作者：
CILIAX, BJ;HEILMAN, C;LEVEY, AI
通讯作者：
LEVEY, AI