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Transgenic mice mimic cardiac hypertrophy in humans

Vanderbilt scientists have created a new strain of mouse that exhibits cardiac hypertrophy an enlargement of the heart similar to that which causes heart failure in millions of Americans each year and may help explain why men are subject to this fatal condition while women are spared until menopause. The new mice were created using genetic engineering techniques that allow researchers to disable specific genes in an animals genome. In this case, the mice were created by knocking out the gene that expresses a protein named FKBP12.6 that binds to special receptors in heart cells that control the release of calcium ions into the cells interior. Regular spikes in calcium concentrations within cardiac muscle cells cause the heart to beat.

What makes these mice particularly interesting, say the researchers, is that they exhibit sex differences in the development of cardiac hypertrophy similar to those in humans. The male mice develop enlarged hearts but the females do not. However, when the females are given a drug that blocks the action of the female hormone, estrogen, their hearts enlarge as well, the scientific team from Vanderbilt and Cornell universities report in the March 21 issue of the journal Nature.

Once people develop severe cardiac hypertrophy, they have about four to five years to live. Its a condition for which there is no cure, says Sidney Fleischer, professor of biological sciences and pharmacology at Vanderbilt. We dont understand the events that take place at the molecular level that cause the heart to become enlarged. If we knew the molecular signals that cause such an enlargement then we should be able to come up with ways to prevent it and perhaps reverse it.

Fleischer led the research effort working with postdoctoral researchers Hong-Bo Xin, who helped initiate the knock-out mouse project, and later with Deng-Sheng Cheng. The Cornell group, led by Michael Kotlikoff and joined by Xin, focused its studies on the changes in the mous
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Contact: David F. Salisbury
david.salisbury@vanderbilt.edu
615-343-6803
Vanderbilt University
20-Mar-2002


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