CAP2 in cardiac conduction, sudden cardiac death and eye development
نویسندگان
چکیده
Sudden cardiac death kills 180,000 to 450,000 Americans annually, predominantly males. A locus that confers a risk for sudden cardiac death, cardiac conduction disease, and a newly described developmental disorder (6p22 syndrome) is located at 6p22. One gene at 6p22 is CAP2, which encodes a cytoskeletal protein that regulates actin dynamics. To determine the role of CAP2 in vivo, we generated knockout (KO) mice. cap2−/cap2− males were underrepresented at weaning and ~70% died by 12 weeks of age, but cap2−/cap2− females survived at close to the expected levels and lived normal life spans. CAP2 knockouts resembled patients with 6p22 syndrome in that mice were smaller and they developed microphthalmia and cardiac disease. The cardiac disease included cardiac conduction disease (CCD) and, after six months of age, dilated cardiomyopathy (DCM), most noticeably in the males. To address the mechanisms underlying these phenotypes, we used Cremediated recombination to knock out CAP2 in cardiomyocytes. We found that the mice developed CCD, leading to sudden cardiac death from complete heart block, but no longer developed DCM or the other phenotypes, including sex bias. These studies establish a direct role for CAP2 and actin dynamics in sudden cardiac death and cardiac conduction disease.
منابع مشابه
Erratum: CAP2 in cardiac conduction, sudden cardiac death and eye development
Sudden cardiac death kills 180,000 to 450,000 Americans annually, predominantly males. A locus that confers a risk for sudden cardiac death, cardiac conduction disease, and a newly described developmental disorder (6p22 syndrome) is located at 6p22. One gene at 6p22 is CAP2, which encodes a cytoskeletal protein that regulates actin dynamics. To determine the role of CAP2 in vivo, we generated k...
متن کاملApical Hypertrophic Cardiomyopathy in a Case with Chest Pain and Family History of Sudden Cardiac Death: A Case Report
Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease, which is caused by a multitude of mutations in genes encoding proteins of the cardiac sarcomere (1). Apical hypertrophic cardiomyopathy (AHCM) is an uncommon type of HCM. The sudden cardiac death is less likely to occur in the patients inflicted with AHCM (2). Herein, we presented the case of a 29-year-old man ...
متن کاملHistomorphological Spectrum of Various Cardiac Changes in Sudden Death: An Autopsy Study
Background and Objectives: In spite of large number of studies conducted so far, sudden cardiac death remains an enigma and relative importance of acute coronary events as a trigger of sudden death is currently unclear. An autopsy study of heart was therefore planned to observe various histomorphological cardiac changes, and to determine the frequency association of acute coronary events and my...
متن کاملDevelopment and Function of the Cardiac Conduction System in Health and Disease
The generation and propagation of the cardiac impulse is the central function of the cardiac conduction system (CCS). Impulse initiation occurs in nodal tissues that have high levels of automaticity, but slow conduction properties. Rapid impulse propagation is a feature of the ventricular conduction system, which is essential for synchronized contraction of the ventricular chambers. When functi...
متن کاملDeficiency of cyclase-associated protein 2 promotes arrhythmias associated with connexin43 maldistribution and fibrosis
INTRODUCTION Cyclase-associated protein 2 (CAP2) plays a major role in regulating the actin cytoskeleton. Since inactivation of CAP2 in a mouse model by a gene trap approach (Cap2 (gt/gt) ) results in cardiomyopathy and increased mortality, we hypothesized that CAP2 has a major impact on arrhythmias and electrophysiological parameters. MATERIAL AND METHODS We performed long-term-ECG recording...
متن کامل