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Inhibition of alveolarization and altered pulmonary mechanics in mice expressing GATA-6

¹Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039; and ²Division of Neonatology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2370

Submitted 20 December 2002 ; accepted in final form 6 August 2003

GATA-6, a member of a family of zinc finger transcription factors, is expressed in epithelial cells of the developing lung. 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-CGATA-6 mice). Although GATA-6 did not alter lung morphology at embryonic day 18.5, defects in alveolar septation were observed early in the neonatal period, and air space enlargement persisted to adulthood. Airway resistance, airway elastance, tissue damping, and tissue elastance were significantly decreased, and lung volumes were significantly increased at 12 wk of age. Normal postnatal morphogenesis of the lung depends upon precise temporal-spatial regulation of GATA-6.

lung; transcription factor; morphogenesis

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