References
Query Results -- Details
MGI Accession ID: MGI:3820771
J Number: J:142246
Other Accession IDs:
Title: Forkhead Box m1 transcription factor is required for perinatal lung function.
Authors: Kalin TV; Wang IC; Meliton L; Zhang Y; Wert SE; Ren X; Snyder J; Bell SM; Graf L Jr; Whitsett JA; Kalinichenko VV
Journal: Proc Natl Acad Sci U S A
Volume: 105
Issue: 49
Date: 2008 Dec 9
Year: 2008
Pages: 19330-5
Review Status: Peer Reviewed
Abstract:
The Forkhead Box m1 (Foxm1 or Foxm1b) transcription factor (previously called HFH-11B, Trident, Win, or MPP2) is an important positive regulator of DNA replication and mitosis in a variety of cell types. Global deletion of Foxm1 in Foxm1(-/-) mice is lethal in the embryonic period, causing multiple abnormalities in the liver, heart, lung, and blood vessels. In the present study, Foxm1 was deleted conditionally in the respiratory epithelium (epFoxm1(-/-)). Surprisingly, deletion of Foxm1 did not alter lung growth, branching morphogenesis, or epithelial proliferation but inhibited lung maturation and caused respiratory failure after birth. Maturation defects in epFoxm1(-/-) lungs were associated with decreased expression of T1-alpha and aquaporin 5, consistent with a delay of type I cell differentiation. Expression of surfactant-associated proteins A, B, C, and D was decreased by deletion of Foxm1. Foxm1 directly bound and induced transcriptional activity of the mouse surfactant protein B and A (Sftpb and Sftpa) promoters in vitro, indicating that Foxm1 is a direct transcriptional activator of these genes. Foxm1 is critical for surfactant homeostasis and lung maturation before birth and is required for adaptation to air breathing.
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