title: Defects in pulmonary vasculature and perinatal lung hemorrhage in mice heterozygous null for the Forkhead Box f1 transcription factor.
abstract: Decreased pulmonary expression of Forkhead Box f1 (Foxf1) transcription factor was associated with lethal alveolar hemorrhage in 55% of the Foxf1 +/- newborn mice. The severity of the pulmonary abnormalities correlates with the levels of Foxf1 mRNA. Defects in alveolarization and vasculogenesis were observed in subsets of the Foxf1 +/- mice with relatively low levels of expression from the normal Foxf1 allele. Lung hemorrhage was coincident with disruption of the mesenchymal-epithelial cell interfaces in the alveolar and bronchiolar regions of the lung parenchyma and was associated with increased apoptosis and reduced surfactant protein B (SP-B) expression. Finally, the lung defect associated with the Foxf1 +/- mutation was accompanied by reduced expression of vascular endothelial growth factor (VEGF), the VEGF receptor 2 (Flk-1), bone morphogenetic protein 4 (Bmp-4), and the transcription factors of the Brachyury T-Box family (Tbx2-Tbx5) and Lung Kruppel-like Factor. Reduction in the level of Foxf1 caused neonatal pulmonary hemorrhage and abnormalities in alveologenesis, implicating this transcription factor in the regulation of mesenchyme-epithelial interaction critical for lung morphogenesis.
authors: University of Illinois at Chicago, College of Medicine, Department of Molecular Genetics, 900 S. Ashland Ave., Chicago, IL 60607-7170, USA.
authors: V V
authors: VV
authors: Kalinichenko
authors: L
authors: L
authors: Lim
authors: D B
authors: DB
authors: Stolz
authors: B
authors: B
authors: Shin
authors: F M
authors: FM
authors: Rausa
authors: J
authors: J
authors: Clark
authors: J A
authors: JA
authors: Whitsett
authors: S C
authors: SC
authors: Watkins
authors: R H
authors: RH
authors: Costa
mesh_terms: D000483:Alleles; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D016228:Endothelial Growth Factors / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism; D051858:Forkhead Transcription Factors; D006470:Hemorrhage; D006579:Heterozygote; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008168:Lung / Q000196:embryology* / Q000378:metabolism* / Q000473:pathology; D008222:Lymphokines / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D008957:Models, Genetic; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D016228:Endothelial Growth Factors; D051858:Forkhead Transcription Factors; C486293:Foxf1 protein, mouse; D008222:Lymphokines; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D015534:Trans-Activators; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D001616:beta-Galactosidase