组织特异性RNA干扰显示，滋养细胞中的WT1表达控制生殖细胞存活和精子发生。
Tissue-specific RNAi reveals that WT1 expression in nurse cells controls germ cell survival and spermatogenesis.
作者信息
Rao Manjeet K, Pham John, Imam J Saadi, MacLean James A, Murali Deepa, Furuta Yasuhide, Sinha-Hikim Amiya P, Wilkinson Miles F
机构信息
Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
出版信息
Genes Dev. 2006 Jan 15;20(2):147-52. doi: 10.1101/gad1367806.
Abstract
Using a novel tissue-specific RNA interference (RNAi) approach that mimics the principle by which naturally occurring microRNAs (miRNA) are made, we demonstrate that the Wilms' tumor 1 (WT1) transcription factor has an essential role in spermatogenesis. Mice depleted of WT1 in Sertoli nurse cells suffered from increased germ cell apoptosis, loss of adherens junctions, disregulation of adherence junction-associated genes, and impaired fertility. These effects were recapitulated in transgenic mice expressing a dominant-negative form of WT1 in Sertoli cells, demonstrating the validity of our RNAi approach. Our results indicate that the tumor suppressor WT1 promotes Sertoli cell-germ cell signaling events driving spermatogenesis.
摘要
我们采用了一种新型的组织特异性RNA干扰（RNAi）方法，该方法模仿了天然存在的微小RNA（miRNA）的生成原理，结果表明，威尔姆斯瘤1（WT1）转录因子在精子发生过程中起着至关重要的作用。在支持细胞中耗尽WT1的小鼠出现生殖细胞凋亡增加、黏附连接丧失、黏附连接相关基因失调以及生育能力受损等情况。在支持细胞中表达显性负性形式WT1的转基因小鼠中也出现了这些效应，证明了我们RNAi方法的有效性。我们的结果表明，肿瘤抑制因子WT1促进支持细胞与生殖细胞之间的信号传导事件，从而推动精子发生。
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