Study published in the Journal of Biological Chemistry

Peter J. Gruber, MD, PhD, 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 factors — proteins 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

Follow up studies to focus on possible parallels between gene functions in mice and human heart development

In people, genes in the GATA family regulate the development of heart muscle in particular structures that divide the left and right sides of the heart. Gruber's team is carrying follow-up studies, investigating how the genes seen in mice may be analogous to genes involved in embryonic heart development in humans. "Although a long way off, greater understanding of biological mechanisms during early heart development may eventually provide useful targets for more accurate diagnosis or personalized treatment of children with congenital heart disease," added Gruber.

Funding for the study

Grants from the National Institutes of Health and the Pliezowicz Family Foundation supported this study. Gruber's co-authors were Manvendra K. Singh, Yan Li, Shanru Li, Diane Zhou, Min Min Lu, Jonathan A. Epstein, and Edward E. Morrisey, all of the University of Pennsylvania; and Ryan M. Cobb, of Children's Hospital. Gruber and Yan Li are on the staff of both institutions.