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Scientists Identify Critical Gene Factor in Heart Development

Researchers announced that they have identified a critical genetic factor in the control of many aspects of heart form and function. Scientists have successfully deleted a genetic factor// , called a microRNA, in animal models to understand the role it plays in cardiovascular differentiation and development.

MicroRNAS, or miRNAs, seem to act as rheostats or "dimmer switches" to fine-tune levels of important proteins in cells. To learn how microRNAs do this, the team led by Dr. Srivastava, deleted the gene responsible for one microRNA in mice and examined the effects of its loss on heart development and maintenance. "Knocking out" a gene is a favorite method for figuring out what a particular gene does in a cell by selectively removing it.

"Development of the heart requires very careful regulation of many factors, and that's one reason that microRNAs are so exciting to us," said Dr. Srivastava, GICD Director. "By knocking out the gene for one miRNA, we could determine exactly what it contributes to that complex process."

MicroRNAs exert their control by stopping protein production after the genes have directed them to be made. Previously, it was thought that all the control was at the level of the genes. Although only 20-22 nucleotides long, the microRNAs bind to the much longer messenger RNAs and prevent their blueprint for building a protein from being used. They typically prevent many messenger RNAs from making proteins and therefore can affect myriad events.

The Gladstone team looked at one particular microRNA, miR-1-2, that was active specifically in the heart. A closely related and redundant microRNA miR-1-1 could not fully compensate for loss of miR-1-2. The team found that loss of miR-1-2 affected many functions in the heart, including heart morphogenesis and control of the number of cells in the heart. For example, half of the mice developed holes in the pumping chambers of the heart, which is the most comm
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