Characterization of sinoatrial node in four conduction system marker mice

Characterization of sinoatrial node in four conduction system marker mice
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DOI:
10.1016/j.yjmcc.2007.02.008
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发表时间:
2007-05-01
影响因子:
5
通讯作者:
Benson, D. W.
Benson, D. W.
中科院分区:
医学2区
文献类型:
--
作者:
Viswanathan, S.;Burch, J. B. E.;Benson, D. W.

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专门的心脏传导系统(CCS)由窦房结(SAN)和房室传导系统(AVCS)组成,房室传导系统包括近端(房室结、希氏束和束支)和远端(浦肯野纤维)。在4只CCS标记小鼠[2只转基因小鼠(cGATA6垂直杆LacZ,CCS垂直杆LacZ)和两个靶向基因敲入(水貂垂直杆LacZ,啤酒花垂直杆LacZ)]中,LacZ基因β-Gal的表达被报道为标记了部分近端和远端的动静脉动静脉癌细胞;该标记在成年SAN中的表达尚不清楚。本研究的主要目的是分析这些标记小鼠在识别窦房结中的作用。根据解剖标志,新鲜解剖成年小鼠的下腔静脉间隔区和室间隔区,包括CCS的所有组成部分并进行切片。用SAN标志物(Cx45、HCN4)进行免疫组织化学鉴定,并与报告基因表达(β-GAL)和工作心肌标志物(Cx40和Cx43)进行比较。在所有四个CCS标记的小鼠中,我们发现在近端和远端的动静脉动静脉中都能观察到β-Gals的表达。然而,在CCS外的工作心肌中存在LacZ基因的表达和/或在SAN中缺乏该报告基因的表达阻碍了这些小鼠的有效利用来识别SAN,这使得我们得出结论,我们研究的四个CCS标记小鼠中没有一个是特异性地标记SAN的。(C)2007 Elsevier Inc.保留所有权利。
The specialized cardiac conduction system (CCS) consists of the sinoatrial node (SAN) and the atrioventricular (AV) conduction system (AVCS), which includes proximal (AV node, bundle of His and bundle branches) and distal (Purkinje fibers) components. In four CCS marker mice [two transgenic (cGATA6 vertical bar lacZ, CCS vertical bar lacZ) and two targeted gene knock-in (minK vertical bar lacZ, Hop vertical bar lacZ)] the expression of the lacZ gene beta-gal) has been reported to mark portions of the proximal and distal AVCS; the expression of this marker in the adult SAN is unknown. The primary objective of this study was to analyze the utility of these marker mice in the identification of the SAN. Intercaval and interventricular septal regions, containing all the components of the CCS, were freshly dissected from adult mice based on the anatomical landmarks and sectioned. Immumohistochemical characterization was performed with SAN markers (Cx45, HCN4), compared to the reporter expression ( beta-gal) and markers of the working myocardium (Cx40 and Cx43). In all four of the CCS marker mice, we found that beta-gal expression is consistently observed in the proximal and distal AVCS. However, the presence of lacZ gene expression in the working myocardium outside the CCS and/or the absence of this reporter expression in the SAN prevent the effective use of these mice to identify the SAN, leading us to conclude that none of the four CCS marker mice we studied specifically mark the SAN. (C) 2007 Elsevier Inc. All rights reserved.