GABAA receptor changes in δ subunit-deficient mice:: Altered expression of α4 and γ2 subunits in the forebrain
GABAA receptor changes in δ subunit-deficient mice:: Altered expression of α4 and γ2 subunits in the forebrain
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DOI：
10.1002/cne.10210
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发表时间：
2002-04-29
影响因子：
2.5
通讯作者：
Houser, CR
中科院分区：
文献类型：
--
作者：
Peng, Z;Hauer, B;Houser, CR
6亚基是五聚体γ-氨基丁酸(GABA)A受体的一个新亚基，它向重组受体传递特殊的药理和功能特性，在介导紧张性抑制中可能特别重要。通过基因打靶技术产生了缺乏8亚基的小鼠，并用免疫组织化学和免疫印迹方法对这些小鼠进行了研究，以确定GABA(A)受体的变化是否仅限于8亚基的缺失，或者其他GABA(A)受体亚基的变化是否也存在于8亚基敲除(Delta-/-)小鼠中。对野生型小鼠的免疫组织化学研究证实，这8个亚基在前脑中的分布有限。6亚基表达中等至高水平的区域包括丘脑中继核、尾壳核、齿状回分子层和大脑皮层外层。在邻近区域，如丘脑网状核、下丘脑和苍白球，几乎没有明显的8亚单位标记。对Delta-/-和野生型小鼠其他亚基表达的比较表明，在Delta-/-小鼠中，GABA(A)受体的α4和Gamma2亚基发生了实质性的变化。在Delta-/-小鼠中，Gamma2亚基表达增加，而Alpha4亚基表达降低。重要的是，A4和Gamma2亚基的改变主要局限于正常表达8亚基的大脑区域。这表明额外的亚基变化与8亚基的丢失直接相关，并可能反映了Delta-/-小鼠GABAA受体亚基组成和功能的局部变化。(C)2002年Wiley-Liss，Inc.
The 6 subunit is a novel subunit of the pentameric gamma-aminobutyric acid (GABA)A receptor that conveys special pharmacological and functional properties to recombinant receptors and may be particularly important in mediating tonic inhibition. Mice that lack the 8 subunit have been produced by gene-targeting technology, and these mice were studied with immunohistochemical and immunoblot methods to determine whether changes in GABA(A) receptors were limited to deletion of the 8 subunit or whether alterations in other GABA(A) receptor subunits were also present in the 8 subunit knockout (delta-/-) mice. Immunohistochemical studies of wild-type mice confirmed the restricted distribution of the 8 subunit in the forebrain. Regions with moderate to high levels of 6 subunit expression included thalamic relay nuclei, caudate-putamen, molecular layer of the dentate gyrus, and outer layers of the cerebral cortex. Virtually no 8 subunit labeling was evident in adjacent regions, such as the thalamic reticular nucleus, hypothalamus, and globus pallidus. Comparisons of the expression of other subunits in delta-/- and wild-type mice demonstrated substantial changes in the alpha4 and gamma2 subunits of the GABA(A) receptor in the delta-/- mice. gamma2 Subunit expression was increased, whereas alpha4 subunit expression was decreased in delta-/- mice. Importantly, alterations of both the a4 and the gamma2 subunits were confined primarily to brain regions that normally expressed the 8 subunit. This suggests that the additional subunit changes are directly linked to loss of the 8 subunit and could reflect local changes in subunit composition and function of GABAA receptors in delta-/- mice. (C) 2002 Wiley-Liss, Inc.