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Publication : Importance of forkhead transcription factor Fkhl18 for development of testicular vasculature.

First Author  Sato Y Year  2008
Journal  Mol Reprod Dev Volume  75
Issue  9 Pages  1361-71
PubMed ID  18288644 Mgi Jnum  J:138911
Mgi Id  MGI:3806783 Doi  10.1002/mrd.20888
Citation  Sato Y, et al. (2008) Importance of forkhead transcription factor Fkhl18 for development of testicular vasculature. Mol Reprod Dev 75(9):1361-71
abstractText  Forkhead transcription factors are characterized by a winged helix DNA binding domain, and the members of this family are classified into 20 subclasses by phylogenetic analyses. Fkhl18 is structurally unique, and is classified into FoxS subfamily. We found Fkhl18 expression in periendothelial cells of the developing mouse fetal testis. In an attempt to clarify its function, we generated mice with Fkhl18 gene disruption. Although KO mice developed normally and were fertile in both sexes, we frequently noticed unusual blood accumulation in the fetal testis. Electron microscopic analysis demonstrated frequent gaps, measuring 100-400 nm, in endothelial cells of blood vessels. These gaps probably represented ectopic apoptosis of testicular periendothelial cells, identified by caspase-3 expression, in KO fetuses. No apoptosis of endothelial cells was noted. Fkhl18 suppressed the transcriptional activity of FoxO3a and FoxO4. Considering that Fas ligand gene expression is activated by Foxs, the elevated activity of Foxs in the absence of Fkhl18 probably explains the marked apoptosis of periendothelial cells in Fkhl18 KO mice.
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