Arrhythmia, a potentially life-threatening disorder whereby the rate or rhythm of the heartbeat causes it to beat too fast, slow or irregularly, affects millions of people worldwide.
The rhythm and rate of the heart is regulated by the cardiac conduction system (CCS), a group of specialized cells in the walls of the heart that send electrical signals from the sinoatrial node in the heart's right atrium or upper chamber to the ventricles or lower chambers, causing them to contract and pump blood.
So far, there is little knowledge about the biologic and genetic mechanisms that control the CCSs structure and function. However, new research in mice has demonstrated that the altered function of a gene called Tbx3 interferes with the development of the CCS, and causes lethal arrhythmias.
The December issue of Proceedings of the National Academy of Sciences early edition reported a study in which researchers from the
Anne M. Moon, M.D., Ph.D., adjunct professor of pediatrics at the U of U School of Medicine, said:
"The cardiac conduction system is very sensitive to Tbx3. Tbx3 is required for the conduction system to develop, mature, and then continue to function properly."
The Tbx3 protein, a transcription factor encoded by the TBX3 gene, has been associated with the development of the heart, but its function has not yet been clearly defined. Moon and her team together with Deborah U. Frank, M.D., Ph.D., discovered that in mice, slight changes in the structure of the Tbx3 gene alter the level of the protein. This process can disable the electrical signal in the sinoatrial node and block the atrioventricular node that conducts electrical signals from the atria to the ventricles, resulting in lethal arrhythmias in embryonic and adult mice.
According to Moon, this discovery has an impact on the likelihood of regenerating functional heart tissue.
Moon states:
"There's a big effort to regenerate heart muscle. But if the muscle can't conduct electrical signals, it's not going to do any good; we also need to be able to regenerate conduction tissues to regulate that muscle."
Aside from arrhythmia, TBX3 gene mutations are also associated with limb malformations in humans with ulnar-mammary syndrome. Ulnar-mammary syndrome is an inherited birth disorder whereby individuals suffer from abnormalities of the bones in the hands and forearms and underdeveloped sweat and mammary glands.
Moon is particularly interested in exploring the way in which Tbx3 regulates the cells' behavior in the cardiac conduction system in her future research. She also wants to establish whether cells with insufficient Tbx3 die or if they transform into other kinds of cells, stating: "It turns out that Tbx3 is a lot more important in the heart than we realized."
Researchers at the
Article reference: Proceedings of the National Academy of Sciences