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In early heart development, genes work in tandem
Date:1/12/2010

Philadelphia, Jan. 12, 2010 Studying genes that regulate early heart development in animals, scientists have solved a puzzle about one gene's role, finding that it acts in concert with a related gene. Their finding contributes to understanding how the earliest stages of heart development may go awry, resulting in congenital heart defects in humans.

Peter J. Gruber, M.D., Ph.D., a cardiothoracic surgeon at The Children's Hospital of Philadelphia, led a study published this week in the Jan. 15 issue of the Journal of Biological Chemistry. Occurring in approximately 1 in 200 children, congenital heart defects represent the most common human birth defect.

"We uncovered a role for the Gata5 gene, a role that has been unappreciated in vertebrate cardiac development," said Gruber. "Gata5 is a gene that is essential to heart development in other animals, such as frogs and zebrafish, but contrary to expectations, deleting this gene seemed to have no effect on the hearts of mammals. We found, however, that in mice, this gene cooperates closely with other genes to affect heart development. It may work similarly in humans."

The Gata5 gene expresses the protein GATA5, which is a member of a family of zinc-finger transcription factorsproteins that act as switches to turn gene activity on or off. Transcription factors regulate how DNA carries its instructions into messenger RNA, and RNA in turn helps produce a specific protein with particular functions in biological processes. The GATA transcription factors carry out important tasks during an organism's development.

Working in mice, Gruber's study team genetically engineered mice in which Gata5 genes were inactive, and found the animals were healthy, with normally functioning hearts. They did find, however, that those mice showed increased expression of another gene in the same family, Gata4, which suggested that Gata4 might compensate for the loss of Gata5.

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Contact: John Ascenzi
Ascenzi@email.chop.edu
267-426-6055
Children's Hospital of Philadelphia
Source:Eurekalert

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