title: Normal lung development and function after Sox9 inactivation in the respiratory epithelium.
abstract: Heterozygous mutations in the human SOX9 gene cause campomelic dysplasia (CD), a skeletal malformation syndrome with various other organ defects. Severely affected CD patients usually die in the neonatal period due to respiratory distress. We analyzed the dynamic expression pattern of Sox9 in the developing mouse lung throughout morphogenesis. To determine a role of Sox9 in lung development and function, Sox9 was specifically inactivated in respiratory epithelial cells of the mouse lung using a doxycycline-inducible Cre/loxP system. Immunohistochemical and RNA analysis demonstrated extensive inactivation of Sox9 in the embryonic stage of lung development as early as embryonic day (E) 12.5. Lung morphogenesis and lung function after birth were not altered. Compensatory upregulation of Sox2, Sox4, Sox8, Sox10, Sox11, and Sox17 was not detected. Although Sox9 is expressed at high levels throughout lung morphogenesis, inactivation of Sox9 from the respiratory epithelial cells does not alter lung structure, postnatal survival, or repair following oxygen injury.
authors.affiliation: Children's Hospital Medical Center, Division of Pulmonary Biology, Cincinnati, Ohio 45229-3039, USA. Anne.Perl@cchmc.org
authors.forename: Anne-Karina T
authors.initials: AK
authors.lastname: Perl
authors.forename: Ralf
authors.initials: R
authors.lastname: Kist
authors.forename: Zhengyuan
authors.initials: Z
authors.lastname: Shan
authors.forename: Gerd
authors.initials: G
authors.lastname: Scherer
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Whitsett
mesh_terms: D000818:Animals; D003433:Crosses, Genetic; D004318:Doxycycline / Q000494:pharmacology; D005260:Female; D017353:Gene Deletion; D006609:High Mobility Group Proteins / Q000235:genetics* / Q000502:physiology; D007150:Immunohistochemistry; D008168:Lung / Q000166:cytology / Q000196:embryology* / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D038081:Organogenesis / Q000235:genetics* / Q000502:physiology; D011247:Pregnancy; D012313:RNA / Q000032:analysis; D020545:Respiratory Mucosa / Q000502:physiology*; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D015533:Transcriptional Activation
chemical_list: D006609:High Mobility Group Proteins; D014157:Transcription Factors; D012313:RNA; D004318:Doxycycline