Foxa2 has an important role in the development of surfactant. It resides in the respiratory epithelial cells, which combines surfactant proteins and lipids (essential fat), which in turn produces surfactant.
Researchers bred mice with and without the Foxa2 gene. When the gene was deleted, the knockout mice developed all the signs and symptoms of respiratory distress syndrome on the first day of life and died within hours of birth. The few knockout mice that did survive, developed asthma-like symptoms and emphysema later in life. On the other hand, when Foxa2 was fully intact, the newborn mice survived normally.
Foxa2 is different from other genes because it is a master gene: it controls how other genes work. For example, in the knockout mice, genes expressed in surfactant proteins and genes involved in lipid metabolism, were directly influenced by the absence of Foxa2.
Researchers found that when the Foxa2 gene was deleted, the Foxa1 gene was expressed more strongly, perhaps in an effort to compensate for the absence of the parent gene, Dr. Whitsett said. Still, the Foxa1 was not strong enough to support the development of sustainable healthy lungs in the mice.
According to the March of Dimes, one in eight infants in the U.S. are born prematurely. Furthermore, approximately 24 percent of all infants born prematurely will die in the first month of life and in most cases, it is as a result of respiratory distress syndrome.
Steroids have become one of the most common courses of treatment for infants with underdeveloped lungs. Steroids work by stimulating lung development, but their use has been associated with side effects, such as cerebral palsy, asthma and bronchitis.
The identification of Foxa2's role in lung developmen
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Contact: Amy Reyes
amy.reyes@cchmc.org
513-636-9684
Cincinnati Children's Hospital Medical Center
27-Sep-2004