EXAMINATION OF ALLOSTERIC SITE OF SEROTONIN TRANSPORTER USING TRANSGENIC MICE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在报告期间，我们检查了小鼠与这种转运蛋白突变的分子和行为相关性，这使我们能够创建一个靶向转基因敲入小鼠，在其中，5-羟色胺转运蛋白中先前描述的突变显著改变了特定抗抑郁药的结合。 转基因构建物的生产已经完成，我们已经成功地创造了一个表达突变SERT多态的敲入鼠系。我们将继续努力完成胚胎干细胞的筛选工作。在细胞系上继续筛选野生型SERT多态的同源重组克隆。我们的研究将继续检查野生型小鼠对西酞普兰急性和慢性剂量的行为反应。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. During the reporting period, we examined the molecular and behavioral correlates of mice with mutations in this transporter, which allowed us to create a targeted transgenic knock-in mouse in which a previously characterized mutation within the serotonin transporter significantly alters the binding for specific antidepressants. Production of the transgenic construct has been completed and we have successfully created a knock-in mouse line that expresses the mutant SERT polymorphism. We continue to work to complete the screening of embryonic stem cells. Screening continues on cell lines for homologous recombinant clones of the wildtype SERT polymorphism. Our studies will continue to examine behavioral responses to acute and chronic citalopram dosing in wild-type mice.