Loss of Sec-1 Family Domain-Containing 1 () Causes Severe Cardiac Defects and Endoplasmic Reticulum Stress in Zebrafish.

Dilated cardiomyopathy (DCM) is a common heart muscle disorder that frequently leads to heart failure, arrhythmias, and death. While DCM is often heritable, disease-causing mutations are identified in only ~30% of cases. In a forward genetic mutagenesis screen, we identified a novel zebrafish mutant, (), characterized by early-onset cardiomyopathy and craniofacial defects.

Titin-related Cardiomyopathy: Is it a Distinct Disease?

Purpose Of Review: Truncating TTN variants (TTNtv) are the most common genetic cause of dilated cardiomyopathy (DCM), but the underlying mechanisms are incompletely understood and effective therapeutic strategies are lacking. Here we review recent data that shed new light on the functional consequences of TTNtv and how these effects may vary with mutation location.

Recent Findings: Whether TTNtv act by haploinsufficiency or dominant negative effects has been hotly debated.

Mechanisms of tv-Related Dilated Cardiomyopathy: Insights from Zebrafish Models.

Dilated cardiomyopathy (DCM) is a common heart muscle disorder characterized by ventricular dilation and contractile dysfunction that is associated with significant morbidity and mortality. New insights into disease mechanisms and strategies for treatment and prevention are urgently needed. Truncating variants in the gene, which encodes the giant sarcomeric protein titin (tv), are the most common genetic cause of DCM, but exactly how tv promote cardiomyocyte dysfunction is not known.

A-Band Titin Truncation in Zebrafish Causes Dilated Cardiomyopathy and Hemodynamic Stress Intolerance.

Background Truncating variants in the TTN gene ( TTNtv) are common in patients with dilated cardiomyopathy (DCM) but also occur in the general population. Whether TTNtv are sufficient to cause DCM or require a second hit for DCM manifestation is an important clinical issue. Methods We generated a zebrafish model of an A-band TTNtv identified in 2 human DCM families in which early-onset disease appeared to be precipitated by ventricular volume overload.

A Langendorff-like system to quantify cardiac pump function in adult zebrafish.

Zebrafish are increasingly used as a vertebrate model to study human cardiovascular disorders. Although heart structure and function are readily visualized in zebrafish embryos because of their optical transparency, the lack of effective tools for evaluating the hearts of older, nontransparent fish has been a major limiting factor. The recent development of high-frequency echocardiography has been an important advance for cardiac assessment, but it necessitates anesthesia and has limited ability to study acute interventions.

Genetics of Atrial Fibrillation: State of the Art in 2017.

Genetic variation is an important determinant of atrial fibrillation (AF) susceptibility. Numerous rare variants in protein-coding sequences of genes have been associated with AF in families and in early-onset cases, and chromosomal loci harbouring common risk variants have been mapped in AF cohorts. Many of these loci are in non-coding regions of the human genome and are thought to contain regulatory sequences that modulate gene expression.

Standardized echocardiographic assessment of cardiac function in normal adult zebrafish and heart disease models.

The zebrafish (Danio rerio) is an increasingly popular model organism in cardiovascular research. Major insights into cardiac developmental processes have been gained by studies of embryonic zebrafish. However, the utility of zebrafish for modeling adult-onset heart disease has been limited by a lack of robust methods for in vivo evaluation of cardiac function.

The two-pore domain potassium channel, TWIK-1, has a role in the regulation of heart rate and atrial size.

The two-pore domain potassium (K(+)) channel TWIK-1 (or K2P1.1) contributes to background K(+) conductance in diverse cell types. TWIK-1, encoded by the KCNK1 gene, is present in the human heart with robust expression in the atria, however its physiological significance is unknown.