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Updated: Nov 10, 2025

Dual-Dye Optical Mapping of Hearts from RyR2R2474S Knock-In Mice of Catecholaminergic Polymorphic Ventricular Tachycardia
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Myocardium-Specific Deletion of Rac1 Causes Ventricular Noncompaction and Outflow Tract Defects

Carmen Leung1, Anish Engineer1, Mella Y Kim1

  • 1Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada.

Journal of Cardiovascular Development and Disease
|April 3, 2021
PubMed

Insights

Rac1 deficiency in heart cells disrupts cardiomyocyte development, leading to congenital heart defects like ventricular septal defects and impaired heart growth. This implicates Rac1 signaling in proper heart formation.

Area of Science:

  • Cardiology
  • Developmental Biology
  • Genetics

Background:

  • Left ventricular noncompaction (LVNC) is a heart muscle disorder linked to arrhythmias and heart failure.
  • Mechanisms of ventricular noncompaction remain unclear despite advances in cardiac development.
  • The small GTPase Rac1 is vital for various developmental processes.

Purpose of the Study:

  • To investigate the specific role of Rac1 in cardiomyocytes during embryonic heart development.
  • To understand how Rac1 deficiency impacts cardiac morphogenesis.

Main Methods:

  • Generated cardiomyocyte-specific Rac1 knockout mice (Rac1) using Nkx2.5-Cre and Rac1 mice.
  • Performed histological analysis on embryonic Rac1 hearts (E12.5-E18.5).
  • Assessed cardiomyocyte morphology, myocardial organization, and cell proliferation rates.

Main Results:

  • Rac1 hearts showed a bifid apex, hypertrabeculation, and thin compact myocardium.
  • Observed congenital heart defects including VSDs and DORV/overriding aorta.
  • Cardiomyocytes were rounded and disorganized; Scrib expression was reduced; cell proliferation decreased.

Conclusions:

  • Rac1 deficiency impairs cardiomyocyte elongation, organization, and heart growth.
  • Rac1 signaling is crucial for outflow tract alignment and compact myocardium development.
  • A spectrum of congenital heart defects arises from Rac1 deficiency in the ventricular myocardium.
Abstract

Keywords:
Rac1cell polaritycompact myocardiumcongenital heart defectsproliferationtrabeculation

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