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选择性 Cre 介导的基因缺失鉴定连接蛋白 43 为支持嗅鞘细胞网络的主要连接蛋白通道。

Selective Cre-mediated gene deletion identifies connexin 43 as the main connexin channel supporting olfactory ensheathing cell networks.

机构信息

CONICET, Instituto de Fisiología y Biofísica Bernardo Houssay (IFIBIO), Neurociencia de Sistemas, Buenos Aires, Argentina.

Universidad de Buenos Aires, Instituto de Fisiología y Biofísica Bernardo Houssay (IFIBIO), Neurociencia de Sistemas, Buenos Aires, Argentina.

出版信息

J Comp Neurol. 2019 May 1;527(7):1278-1289. doi: 10.1002/cne.24628. Epub 2019 Jan 21.

Abstract

Many functions of glial cells depend on the formation of selective glial networks mediated by gap junctions formed by members of the connexin family. Olfactory ensheathing cells (OECs) are specialized glia associated with olfactory sensory neuron axons. Like other glia, they form selective networks, however, the connexins that support OEC connectivity in vivo have not been identified. We used an in vivo mouse model to selectively delete candidate connexin genes with temporal control from OECs and address the physiological consequences. Using this model, we effectively abolished the expression of connexin 43 (Cx43) in OECs in both juvenile and adult mice. Cx43-deleted OECs exhibited features consistent with the loss of gap junctions including reduced membrane conductance, largely reduced sensitivity to the gap junction blocker meclofenamic acid and loss of dye coupling. This indicates that Cx43, a typically astrocytic connexin, is the main connexin forming functional channels in OECs. Despite these changes in functional properties, the deletion of Cx43 deletion did not alter the density of OECs. The strategy used here may prove useful to delete other candidate genes to better understand the functional roles of OECs in vivo.

摘要

许多神经胶质细胞的功能依赖于缝隙连接形成的选择性神经胶质网络,而缝隙连接则由连接蛋白家族的成员介导。嗅鞘细胞(OECs)是与嗅觉感觉神经元轴突相关的特化神经胶质细胞。与其他神经胶质细胞一样,它们形成选择性网络,但支持 OEC 连接的连接蛋白在体内尚未确定。我们使用体内小鼠模型,具有时间控制的条件下从 OEC 中选择性地删除候选连接蛋白基因,并研究其生理后果。使用该模型,我们有效地消除了幼年和成年小鼠 OEC 中连接蛋白 43(Cx43)的表达。Cx43 缺失的 OEC 表现出与缝隙连接丧失一致的特征,包括膜电导降低、对缝隙连接阻滞剂甲芬那酸的敏感性大大降低以及染料偶联丧失。这表明 Cx43,一种典型的星形胶质细胞连接蛋白,是在 OEC 中形成功能性通道的主要连接蛋白。尽管功能特性发生了这些变化,但 Cx43 的缺失并未改变 OEC 的密度。这里使用的策略可能有助于删除其他候选基因,以更好地理解 OEC 在体内的功能作用。

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