Limitations of the Avp-IRES2-Cre (JAX #023530) and Vip-IRES-Cre (JAX #010908) Models for Chronobiological Investigations
Limitations of the Avp-IRES2-Cre (JAX #023530) and Vip-IRES-Cre (JAX #010908) Models for Chronobiological Investigations
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DOI：
10.1177/0748730419871184
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发表时间：
2019-08-27
影响因子：
3.5
通讯作者：
Cheng, Hai-Ying Mary
中科院分区：
文献类型：
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作者：
Cheng, Arthur H.;Fung, Samuel W.;Cheng, Hai-Ying Mary
哺乳动物的主要昼夜节律起搏器，视交叉上核（SCN），表达了许多促进细胞间同步的神经肽，有助于产生连贯的输出到整个身体的外周时钟。特别是，精氨酸加压素（AVP）和血管活性肠肽（VIP）表达神经元已被公认为SCN内的关键亚群，因此一直是许多时间生物学研究的焦点。在这里，我们分析了2个流行的转基因小鼠品系的神经肽表达通常用于指导或限制铬介导的重组AVP和VIP能神经元。Avp-IRES 2-Cre（JAX#023530）和Vip-IRES-Cre（JAX#010908）“驱动”小鼠品系分别在内源Avp或Vip基因的控制下表达Cre重组酶，允许科学家以细胞类型特异性方式消除其感兴趣的基因或过表达转基因。虽然这些对于时间生物学家和其他研究AVP和VIP能神经元的科学家来说是潜在的非常强大的工具，但我们发现，当将IRES（2）-Cre盒插入神经肽编码基因位点的下游时，这些小鼠中的神经肽表达显著降低。IRES（2）-Cre盒插入对神经肽表达的影响可能是许多实验设计中的混杂因素。我们的研究结果表明，在使用这些小鼠模型时必须非常谨慎，以避免对经验结果的误解。
The principal circadian pacemaker in mammals, the suprachiasmatic nucleus (SCN), expresses a number of neuropeptides that facilitate intercellular synchrony, helping to generate coherent outputs to peripheral clocks throughout the body. In particular, arginine vasopressin (AVP)- and vasoactive intestinal peptide (VIP)-expressing neurons have been recognized as crucial subpopulations within the SCN and have thus been the focus of many chronobiological studies. Here, we analyze the neuropeptide expression of 2 popular transgenic mouse strains commonly used to direct or restrict Cre-mediated recombination to AVP- and VIP-ergic neurons. The Avp-IRES2-Cre (JAX #023530) and Vip-IRES-Cre (JAX #010908) "driver" mouse strains express the Cre recombinase under the control of the endogenous Avp or Vip gene, respectively, allowing scientists either to ablate their gene of interest or to overexpress a transgene in a cell type-specific manner. Although these are potentially very powerful tools for chronobiologists and other scientists studying AVP- and VIP-ergic neurons, we found that neuropeptide expression in these mice is significantly decreased when an IRES(2)-Cre cassette is inserted downstream of the neuropeptide-encoding gene locus. The impact of IRES(2)-Cre cassette insertion on neuropeptide expression may be a confounding factor in many experimental designs. Our findings suggest that extreme caution must be exercised when using these mouse models to avoid misinterpretation of empirical results.