Characterization of sinoatrial node in four conduction system marker mice

Area of Science:

• Cardiovascular Research
• Developmental Biology
• Genetics

Background:

• The cardiac conduction system (CCS) is crucial for coordinated heartbeats, comprising the sinoatrial node (SAN) and atrioventricular conduction system (AVCS).
• Understanding CCS development and function relies on accurate identification of its components using genetic markers.
• Previous studies indicated lacZ reporter gene expression in parts of the AVCS in specific mouse models, but its utility for SAN identification remained unassessed.

Purpose of the Study:

• To evaluate the effectiveness of four CCS marker mouse models (cGATA6|lacZ, CCS|lacZ, minK|lacZ, Hop|lacZ) for specifically identifying the adult sinoatrial node (SAN).
• To compare lacZ reporter gene expression with known SAN and working myocardium markers.

Main Methods:

• Dissection of adult mouse heart regions containing the CCS (intercaval and interventricular septal areas).
• Immunohistochemical analysis to detect beta-galactosidase (reporter) expression.
• Comparison of reporter expression with established SAN markers (Cx45, HCN4) and working myocardium markers (Cx40, Cx43).

Main Results:

• All four CCS marker mouse models consistently showed lacZ gene (beta-gal) expression in the proximal and distal AVCS.
• Expression of the lacZ reporter was detected in the working myocardium outside the CCS in these models.
• Crucially, lacZ expression was absent in the SAN in all four evaluated mouse models.

Conclusions:

• None of the four CCS marker mouse models studied (cGATA6|lacZ, CCS|lacZ, minK|lacZ, Hop|lacZ) can be effectively used to specifically identify the sinoatrial node (SAN).
• The observed expression patterns, including expression in non-CCS regions and absence in the SAN, preclude their use as reliable SAN markers.