WT-1 IS REQUIRED FOR EARLY KIDNEY DEVELOPMENT
WT-1 IS REQUIRED FOR EARLY KIDNEY DEVELOPMENT
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DOI：
10.1016/0092-8674(93)90515-r
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发表时间：
1993-08-27
期刊：
影响因子：
64.5
通讯作者：
JAENISCH, R
中科院分区：
文献类型：
--
作者：
KREIDBERG, JA;SARIOLA, H;JAENISCH, R
在人类中，WT-1肿瘤抑制基因的种系突变与Wilms肿瘤和泌尿生殖系统畸形有关。为了建立一个用于泌尿生殖发育分子分析的模型系统，我们在小鼠胚胎干细胞中通过基因靶向将一个突变引入小鼠WT-1肿瘤抑制基因。突变导致纯合子的胚胎致死，突变胚胎的检查显示肾脏和性腺发育衰竭。在妊娠第11天，后肾囊胚细胞发生凋亡，输尿管芽不能从Wolffian管中生长出来，导致后肾形成的诱导事件没有发生。此外，这种突变还会导致间皮层、心脏和肺部发育异常。我们的研究结果确立了WT-1在早期泌尿生殖发育中的关键作用。
In humans, germline mutations of the WT-1 tumor suppressor gene are associated with both Wilms' tumors and urogenital malformations. To develop a model system for the molecular analysis of urogenital development, we introduced a mutation into the murine WT-1 tumor suppressor gene by gene targeting in embryonic stem cells. The mutation resulted in embryonic lethality in homozygotes, and examination of mutant embryos revealed a failure of kidney and gonad development. Specifically, at day 11 of gestation, the cells of the metanephric blastema underwent apoptosis, the ureteric bud failed to grow out from the Wolffian duct, and the inductive events that lead to formation of the metanephric kidney did not occur. In addition, the mutation caused abnormal development of the mesothelium, heart, and lungs. Our results establish a crucial role for WT-1 in early urogenital development.