Mouse Model Shows How a Gene Deletion Enables Regeneration of Adult Heart Muscle

Researchers have identified a gene required by the embryo for heart development but found that its continued expression turned off the ability of mature heart muscle to regenerate.

The Meis1 (Meis homeobox 1) gene codes for a transcription factor required for normal cardiac development, but its role in cardiomyocytes (heart muscle cells) had not been determined. To understand the function of Meis1 investigators at the University of Texas Southwestern Medical Center (Dallas, USA) genetically engineered a line of mice lacking this gene.

They reported in the April 17, 2013, online edition of the journal Nature that cardiomyocytes taken from these animals were able to regenerate for much longer than the seven days after birth that is the case for cardiomyocytes from normal mice. Furthermore, deletion of the Meis1 gene was sufficient to reactivate cardiomyocyte mitosis in the hearts of adult mice with no deleterious effect on cardiac function. In contrast, overexpression of Meis1 in cardiomyocytes decreased neonatal myocyte proliferation and inhibited neonatal heart regeneration.

“We found that the activity of the Meis1 gene increases significantly in heart cells soon after birth, right around the time heart muscle cells stop dividing. Based on this observation we asked a simple question: If the Meis1 gene is deleted from the heart, will heart cells continue to divide through adulthood? The answer is yes,” said senior author Dr. Hesham Sadek, assistant professor of internal medicine at the University of Texas Southwestern Medical Center. “Meis1 is a transcription factor, which acts like a software program that has the ability to control the function of other genes. In this case, we found that Meis1 controls several genes that normally act as brakes on cell division. As such, Meis1 could possibly be used as an on/off switch for making adult heart cells divide. If done successfully, this ability could introduce a new era in treatment for heart failure.”

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University of Texas Southwestern Medical Center