Mouse Model Promotes Study of Heart Failure Genes

Heart disease researchers have used a mouse model to identify groups of genes that influence the severity of heart failure and the likelihood of recovery.

Investigators at Duke University Medical Center (Durham, NC, USA) mated males of a mouse strain with mutations that conferred a very reproducible and severe form of heart failure with females from a healthy mouse strain. By screening the genomes of the offspring, some of which suffered heart failure while others did not, the investigators identified genetic regions that modified the severity of heart failure.

Their paper, published in the December 1, 2003, issue of Human Molecular Genetics, described two regions, one on chromosome 13 and another on chromosome 18, that were linked to heart function and survival with heart failure. An additional region on chromosome 2 affected cardiac function with no effect on survival, while another on chromosome 4 influenced survival without impacting heart function in mice with heart failure.

"Our goal is to find novel genes that modify human heart failure by letting the mouse point us in the right direction,” explained senior author Dr. Howard Rockman, a cardiologist at Duke University Medical Center. "Such genes would provide us the means to identify those heart failure patients having subtle genetic differences that make them more susceptible to poor outcomes. That some genes affect cardiac function without affecting survival and vice versa suggests that distinct genes may underlie the gradual decline in heart function characteristic of heart failure and the risk of sudden death associated with the disease.”