Importance of forkhead transcription factor Fkhl18 for development of testicular vasculature
Importance of forkhead transcription factor Fkhl18 for development of testicular vasculature
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DOI：
10.1002/mrd.20888
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发表时间：
2008-09
影响因子：
2.5
通讯作者：
Yuko Sato;Takashi Baba;M. Zubair;K. Miyabayashi;Y. Toyama;M. Maekawa;A. Owaki;H. Mizusaki;T. Sawamura;K. Toshimori;K. Morohashi;Y. Katoh-Fukui
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作者：
Yuko Sato;Takashi Baba;M. Zubair;K. Miyabayashi;Y. Toyama;M. Maekawa;A. Owaki;H. Mizusaki;T. Sawamura;K. Toshimori;K. Morohashi;Y. Katoh-Fukui
叉头转录因子以一个带翼螺旋的DNA结合域为特征，经系统发育分析，叉头转录因子家族成员可分为20个亚类。Fkhl18结构独特，属于FoxS亚家族。我们发现Fkhl18在发育中的小鼠胎儿睾丸内皮细胞中表达。为了阐明其功能，我们制造了Fkhl18基因破坏的小鼠。虽然KO小鼠发育正常，雌雄均可生育，但我们经常注意到胎儿睾丸中异常的血液积聚。电镜分析显示血管内皮细胞中有100 - 400nm的间隙。这些间隙可能代表了KO胎儿睾丸内皮细胞的异位凋亡，通过caspase‐3表达鉴定。未见内皮细胞凋亡。Fkhl18抑制FoxO3a和FoxO4的转录活性。考虑到Fas配体基因表达被Foxs激活，Foxs活性升高在Fkhl18缺失的情况下可能解释了Fkhl18 KO小鼠内皮周细胞明显凋亡的原因。摩尔。天线转换开关。开发与应用，2008。©2008 Wiley‐Liss, Inc。
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. Mol. Reprod. Dev. 75: 1361–1371, 2008. © 2008 Wiley‐Liss, Inc.