scholarly journals Inducible gene deletion in the entire cardiac conduction system using Hcn4-CreERT2 BAC transgenic mice

genesis ◽  
2013 ◽  
Vol 52 (2) ◽  
pp. 134-140 ◽  
Author(s):  
Meng Wu ◽  
Siwu Peng ◽  
Yong Zhao
2008 ◽  
Vol 45 (1) ◽  
pp. 62-69 ◽  
Author(s):  
Evelyn Hoesl ◽  
Juliane Stieber ◽  
Stefan Herrmann ◽  
Susanne Feil ◽  
Elisabeth Tybl ◽  
...  

Development ◽  
2001 ◽  
Vol 128 (10) ◽  
pp. 1785-1792 ◽  
Author(s):  
S. Rentschler ◽  
D.M. Vaidya ◽  
H. Tamaddon ◽  
K. Degenhardt ◽  
D. Sassoon ◽  
...  

The cardiac conduction system is a complex network of cells that together orchestrate the rhythmic and coordinated depolarization of the heart. The molecular mechanisms regulating the specification and patterning of cells that form this conductive network are largely unknown. Studies in avian models have suggested that components of the cardiac conduction system arise from progressive recruitment of cardiomyogenic progenitors, potentially influenced by inductive effects from the neighboring coronary vasculature. However, relatively little is known about the process of conduction system development in mammalian species, especially in the mouse, where even the histological identification of the conductive network remains problematic. We have identified a line of transgenic mice where lacZ reporter gene expression delineates the developing and mature murine cardiac conduction system, extending proximally from the sinoatrial node to the distal Purkinje fibers. Optical mapping of cardiac electrical activity using a voltage-sensitive dye confirms that cells identified by the lacZ reporter gene are indeed components of the specialized conduction system. Analysis of lacZ expression during sequential stages of cardiogenesis provides a detailed view of the maturation of the conductive network and demonstrates that patterning occurs surprisingly early in embryogenesis. Moreover, optical mapping studies of embryonic hearts demonstrate that a murine His-Purkinje system is functioning well before septation has completed. Thus, these studies describe a novel marker of the murine cardiac conduction system that identifies this specialized network of cells throughout cardiac development. Analysis of lacZ expression and optical mapping data highlight important differences between murine and avian conduction system development. Finally, this line of transgenic mice provides a novel tool for exploring the molecular circuitry controlling mammalian conduction system development and should be invaluable in studies of developmental mutants with potential structural or functional conduction system defects.


Diagnostics ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1323
Author(s):  
Giulia Ottaviani ◽  
Graziella Alfonsi ◽  
Simone G. Ramos ◽  
L. Maximilian Buja

A retrospective study was conducted on pathologically diagnosed arrhythmogenic cardiomyopathy (ACM) from consecutive cases over the past 34 years (n = 1109). The anatomo-pathological analyses were performed on 23 hearts diagnosed as ACM (2.07%) from a series of 1109 suspected cases, while histopathological data of cardiac conduction system (CCS) were available for 15 out of 23 cases. The CCS was removed in two blocks, containing the following structures: Sino-atrial node (SAN), atrio-ventricular junction (AVJ) including the atrio-ventricular node (AVN), the His bundle (HB), the bifurcation (BIF), the left bundle branch (LBB) and the right bundle branch (RBB). The ACM cases consisted of 20 (86.96%) sudden unexpected cardiac death (SUCD) and 3 (13.04%) native explanted hearts; 16 (69.56%) were males and 7 (30.44%) were females, ranging in age from 5 to 65 (mean age ± SD, 36.13 ± 16.06) years. The following anomalies of the CCS, displayed as percentages of the 15 ACM SUCD cases in which the CCS has been fully analyzed, have been detected: Hypoplasia of SAN (80%) and/or AVJ (86.67%) due to fatty-fibrous involvement, AVJ dispersion and/or septation (46.67%), central fibrous body (CFB) hypoplasia (33.33%), fibromuscular dysplasia of SAN (20%) and/or AVN (26.67%) arteries, hemorrhage and infarct-like lesions of CCS (13.33%), islands of conduction tissue in CFB (13.33%), Mahaim fibers (13.33%), LBB block by fibrosis (13.33%), AVN tongue (13.33%), HB duplicity (6.67%%), CFB cartilaginous meta-hyperplasia (6.67%), and right sided HB (6.67%). Arrhythmias are the hallmark of ACM, not only from the fatty-fibrous disruption of the ventricular myocardium that accounts for reentrant ventricular tachycardia, but also from the fatty-fibrous involvement of CCS itself. Future research should focus on application of these knowledge on CCS anomalies to be added to diagnostic criteria or at least to be useful to detect the patients with higher sudden death risks.


2013 ◽  
Vol 98 (3) ◽  
pp. 504-514 ◽  
Author(s):  
Angel J. de la Rosa ◽  
Jorge N. Domínguez ◽  
David Sedmera ◽  
Bara Sankova ◽  
Leif Hove-Madsen ◽  
...  

2003 ◽  
Vol 12 (2) ◽  
pp. 77-81 ◽  
Author(s):  
Giulia Ottaviani ◽  
Luigi Matturri ◽  
Lino Rossi ◽  
Dan Jones

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