Inhibition of alveolarization and altered pulmonary mechanics in mice expressing GATA-6.
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.
Liu
Cong
C
Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
Ikegami
Machiko
M
Stahlman
Mildred T
MT
Dey
Chitta R
CR
Whitsett
Jeffrey A
JA
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D050993:GATA6 Transcription Factor; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D011650:Pulmonary Alveoli / Q000166:cytology / Q000254:growth & development* / Q000502:physiology*; D011652:Pulmonary Circulation / Q000502:physiology; D037721:Pulmonary Surfactant-Associated Protein C / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D020545:Respiratory Mucosa / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; D050993:GATA6 Transcription Factor; C494759:GATA6 protein, human; C494760:Gata6 protein, mouse; D037721:Pulmonary Surfactant-Associated Protein C; D012333:RNA, Messenger; D014157:Transcription Factors