Knock-In Mouse Models to Investigate the Functions of Opioid Receptors in vivo.
Knock-In Mouse Models to Investigate the Functions of Opioid Receptors in vivo.
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DOI：
10.3389/fncel.2022.807549
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发表时间：
2022
影响因子：
5.3
通讯作者：
Gendron L
中科院分区：
文献类型：
--
作者：
Degrandmaison J;Rochon-Haché S;Parent JL;Gendron L
由于它们的低表达水平、复杂的多通道跨膜结构以及目前缺乏高度特异性的抗体，内源性G蛋白偶联受体（GPCR）的评估仍然具有挑战性。虽然大多数关于其功能的研究都是在过表达受体的异源系统中进行的，但基因工程方法的最新进展已经允许产生几种独特的小鼠模型。这些动物被证明是有用的，以调查潜在的GPCR的生理功能，包括其内源性表达，分布，相互作用组，和运输过程的许多方面。阿片肽受体（OPr）在神经系统中具有重要的药理学意义和中枢作用，常被认为是研究GPCR调控机制的原型受体。尽管迄今为止只产生了少数GPCR敲入小鼠品系，但OPr在20多种不同的敲入模型中得到了惊人的良好代表，其中一半以上是在过去5年内开发的。在这篇综述中，我们描述了武器库的OPr（μ-，δ-和κ-阿片类药物），以及阿片类药物相关的痛敏素/FQ（NOP）受体敲入小鼠模型，已在过去几年中产生的。我们进一步强调了这些模型对我们理解OPr调节的体内机制的宝贵贡献，这些机制可以被转换为任何其他GPCR，以及这些工具的局限性，未来前景和可能性。
Due to their low expression levels, complex multi-pass transmembrane structure, and the current lack of highly specific antibodies, the assessment of endogenous G protein-coupled receptors (GPCRs) remains challenging. While most of the research regarding their functions was performed in heterologous systems overexpressing the receptor, recent advances in genetic engineering methods have allowed the generation of several unique mouse models. These animals proved to be useful to investigate numerous aspects underlying the physiological functions of GPCRs, including their endogenous expression, distribution, interactome, and trafficking processes. Given their significant pharmacological importance and central roles in the nervous system, opioid peptide receptors (OPr) are often referred to as prototypical receptors for the study of GPCR regulatory mechanisms. Although only a few GPCR knock-in mouse lines have thus far been generated, OPr are strikingly well represented with over 20 different knock-in models, more than half of which were developed within the last 5 years. In this review, we describe the arsenal of OPr (mu-, delta-, and kappa-opioid), as well as the opioid-related nociceptin/orphanin FQ (NOP) receptor knock-in mouse models that have been generated over the past years. We further highlight the invaluable contribution of such models to our understanding of the in vivo mechanisms underlying the regulation of OPr, which could be conceivably transposed to any other GPCR, as well as the limitations, future perspectives, and possibilities enabled by such tools.
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影响因子：
3.5
作者：
BUNZOW, JR;SAEZ, C;GRANDY, DK
通讯作者：
GRANDY, DK
影响因子：
3.4
作者：
Bailly, Julie;Del Rossi, Natalie;Kieffer, Brigitte L
通讯作者：
Kieffer, Brigitte L
DOI：
10.1124/jpet.108.146969
发表时间：
2009-04-01
影响因子：
3.5
作者：
Codd, Ellen E.;Carson, John R.;Flores, Christopher M.
通讯作者：
Flores, Christopher M.
影响因子：
56.9
作者：
Bohn, LM;Lefkowitz, RJ;Lin, FT
通讯作者：
Lin, FT
影响因子：
2.5
作者：
Cahill, CM;McClellan, KA;Beaudet, A
通讯作者：
Beaudet, A