Targeting Homer genes using adeno-associated viral vector: lessons learned from behavioural and neurochemical studies.
Targeting Homer genes using adeno-associated viral vector: lessons learned from behavioural and neurochemical studies.
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DOI：
10.1097/fbp.0b013e32830c369f
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发表时间：
2008-09
影响因子：
1.6
通讯作者：
Szumlinski KK
中科院分区：
文献类型：
--
作者：
Klugmann M;Szumlinski KK
超过十年的体外数据支持突触后支架蛋白Homer家族成员在调节谷氨酸突触功能结构中的关键作用。对荷马基因敲除小鼠的早期研究表明，荷马基因产物在正常的中皮质边缘谷氨酸传递及其相关行为中起着必要的作用。携带cDNA或短发夹RNA的腺相关病毒载体的出现，使得特异性Homer亚型能够定向靶向大脑中的神经元。这种方法使我们的研究小组能够解决与传统敲除小鼠相关的发育问题，确认不同的Homer亚型在调节体内谷氨酸传递以及介导各种行为过程中的积极作用。本文综述了我们在啮齿动物中使用腺相关病毒载体介导的Homer神经元靶向研究的现有数据，暗示该蛋白家族与药物和酒精成瘾、学习/记忆和情绪处理有关。
Over a decade of in-vitro data support a critical role for members of the Homer family of postsynaptic scaffolding proteins in regulating the functional architecture of glutamate synapses. Earlier studies of Homer knockout mice indicated a necessary role for Homer gene products in normal mesocorticolimbic glutamate transmission and behaviours associated therewith. The advent of adeno-associated viral vectors carrying cDNA for, or short hairpin RNA against, specific Homer isoforms enabled the site-directed targeting of Homers to neurons in the brain. This approach has allowed our groups to address developmental issues associated with conventional knockout mice, to confirm active roles for distinct Homer isoforms in regulating glutamate transmission in vivo, as well as in mediating a variety of behavioural processes. This review summarizes the existing data derived from our studies using adeno-associated viral vector-mediated neuronal targeting of Homer in rodents, implicating this family of proteins in drug and alcohol addiction, learning/memory and emotional processing.