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Am J Physiol Lung Cell Mol Physiol (August 8, 2003). doi:10.1152/ajplung.00443.2002
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Submitted on December 20, 2002
Accepted on August 6, 2003

INHIBITION OF ALVEOLARIZATION AND ALTERED PULMONARY MECHANICS IN MICE EXPRESSING GATA-6

Cong Liu1, Machiko Ikegami1, Mildred T. Stahlman2, Chitta R. Dey1, and Jeffrey A. Whitsett1*

1 Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
2 Division of Neonatology, Vanderbilt University School of Medicine, Nashville, TN, USA

* To whom correspondence should be addressed. E-mail: jeff.whitsett{at}cchmc.org.

GATA-6, a member of a family of zinc finger transcription factors, is expressed in epithelial cells of the developing lung. In order to further assess the role of GATA-6 in lung morphogenesis, GATA-6 was expressed in respiratory epithelial cells of the developing mouse lung under control of the surfactant protein C promoter (hSP-C-GATA-6 mice). While GATA-6 did not alter lung morphology at E18.5, defects in alveolar septation were observed early in the neonatal period and airspace enlargement persisted to adulthood. Airway resistance, airway elastance, tissue damping and tissue elastance were significantly decreased and lung volumes were significantly increased at 12 weeks of age. Normal postnatal morphogenesis of the lung depends upon precise temporal-spatial regulation of GATA-6.




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