Transgenic Mice Created By Researchers May Shed Light On Human Heart Disease

A University of Colorado at Boulder research team has created several strains of transgenic mice that carry gene mutations for a heart disease that has been shown to be the leading cause of sudden death in young athletes.

Known as hypertrophic cardiomyopathy, the genetic disease is marked by significant thickening of the heart muscle, said Leslie Leinwand, chair of CU-Boulder's molecular, cellular and developmental biology department who is spearheading the research effort. The disease can obstruct blood flow in heart ventricles, lessening their ability to pump blood into the arteries.

"This is a difficult disease to diagnose," said Leinwand. "While symptoms can include shortness of breath, dizziness and chest pain, often the first sign of the disease is death."

Although the most frequent cause of the disease has been shown to be a mutation on a tiny portion of a single gene that produces the protein myosin, it is not known why the myosin gene causes mortality, she said. "We have created these transgenic mice to help us understand the biological processes and hopefully test new therapeutic agents."

Myosin is a major component of muscle tissue and "molecular motor" that creates the energy and motion to allow heart contractions to occur.

Healthy humans have two copies of the normal gene for myosin while people with the disease have a mutated form, just as the mice do, said Leinwand. To create a transgenic mouse, the researchers added a mutated myosin gene to the genetic material of a normal mouse, which was taken up randomly by one of its chromosomes.

In humans and mice, healthy heart muscle is very organized and densely packed with structural protein that allows it to contract, she said. But in heart muscle carrying the mutant form of the myosin gene, the normal, parallel alignment of muscle cells is lost and the c

Contact: Leslie Leinwand
University of Colorado at Boulder

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