Analyzing the validity of GalR1 and GalR2 antibodies using knockout mice.

Analyzing the validity of GalR1 and GalR2 antibodies using knockout mice.
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DOI:
10.1007/s00210-009-0394-z
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发表时间:
2009-04
影响因子:
3.6
通讯作者:
Bartfai, Tamas
Bartfai, Tamas
中科院分区:
医学4区
文献类型:
--
作者:
Lu, Xiaoying;Bartfai, Tamas
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g蛋白偶联受体(gpcr)是最大的细胞表面受体家族,是治疗各种人类疾病的主要药物靶点。然而,缺乏能够识别内源性gpcr的敏感和选择性抗体阻碍了这类受体的研究进展。GalR1至GalR3是神经肽galanine的gpcr,是癫痫发作、阿尔茨海默病、抑郁和焦虑以及疼痛和代谢综合征的潜在药物靶点;因此,确定丙氨酸受体的细胞和亚细胞定位具有很高的意义。几种针对丙氨酸受体的抗体目前可从商业或学术来源获得。我们已经在各自敲除小鼠的组织上测试了几种GalR1和GalR2抗体。出乎意料的是,野生型和敲除小鼠的免疫反应模式是相同的,这表明目前的GalR1和GalR2抗体,在标准的免疫检测条件下,可能不适合定位受体。这些发现表明,在使用针对丙氨酸受体的抗体时要采取预防措施。
G-protein-coupled receptors (GPCRs) comprise the largest family of cell surface receptors and are the major drug targets for the treatment of various human diseases. The lack of sensitive and selective antibodies capable of recognizing endogenous GPCRs, however, hampers the progress of research on this class of receptors. GalR1 through GalR3, GPCRs for the neuropeptide galanin, are potential drug targets for seizure, Alzheimer's disease, depression and anxiety, as well as pain and metabolic syndrome; therefore, determining the cellular and subcellular localization of galanin receptors is of high interest. Several antibodies raised against galanin receptors are currently available from commercial or academic sources. We have tested several antibodies to GalR1 and GalR2 on tissues from respective knockout mice. Unexpectedly, the immunoreactivity patterns are the same in wild type and in knockout mice, suggesting that current GalR1 and GalR2 antibodies, under standard immunodection conditions, might not be suitable for mapping the receptors. These findings argue for taking precaution when using antibodies to galanin receptors.
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