A molecular genetic approach to uncovering the differential functions of dopamine D2 receptor isoforms.
A molecular genetic approach to uncovering the differential functions of dopamine D2 receptor isoforms.
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揭示多巴胺 D2 受体亚型差异功能的分子遗传学方法。
DOI：
10.1007/978-1-62703-251-3_11
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发表时间：
2013
影响因子：
--
通讯作者：
Wang Yanyan
中科院分区：
文献类型：
--
作者：
浜之上 誠;森岡 和仁;緒方 徹;中嶋 一行;高松 研;Wang Yanyan
多巴胺D2受体（D2R）活性的改变与几种神经和精神疾病有关，包括精神分裂症、帕金森病、亨廷顿病、图雷特综合征、注意力缺陷多动障碍（ADHD）和药物成瘾。D2R有两种亚型，长型（D2LR）和短型（D2SR）。人们对每种D2 R亚型的具体功能知之甚少，主要是因为没有亚型选择性药理学药物。使用同源重组，我们已经产生了D2LR敲除（KO）小鼠。D2LR KO小鼠完全缺乏D2LR，但仍以与野生型（WT）小鼠中的总D2R水平相似的水平表达功能性D2SR。D2LR通常是WT小鼠中表达的主要同种型。我们发现，D2LR KO小鼠表现出许多不同于WT小鼠的稳健的行为表型，表明D2LR和D2SR具有不同的功能。在本章中，我们描述了D2LR KO小鼠的产生和表征。这种遗传学方法提供了一个有价值的研究工具，以调查个别D2R亚型在哺乳动物中枢神经系统（CNS）的功能作用。
Alterations in the activity of the dopamine D2 receptor (D2R) have been implicated in several neurological and psychiatric disorders, including schizophrenia, Parkinson’s disease, Huntington’s disease, Tourette syndrome, attention-deficit hyperactivity disorder (ADHD), and drug addiction. Two isoforms of D2R, long form (D2LR) and short form (D2SR), have been identified. The specific function of each D2R isoform is poorly understood, primarily because isoform-selective pharmacological agents are not available. Using homologous recombination, we have generated D2LR knockout (KO) mice. D2LR KO mice are completely deficient in D2LR, but still express functional D2SR at a level similar to the total D2R level in wild-type (WT) mice. D2LR is generally the predominant isoform expressed in WT mice. We showed that D2LR KO mice displayed a number of robust behavioral phenotypes distinct from WT mice, indicating that D2LR and D2SR have differential functions. In this chapter we describe the generation and characterization of the D2LR KO mouse. This genetic approach provides a valuable research tool to investigate the functional role of individual D2R isoforms in the mammalian central nervous system (CNS).