Disruption of Gen1 Causes Congenital Anomalies of the Kidney and Urinary Tract in Mice

نویسندگان

  • Herui Wang
  • Chi Zhang
  • Xiaowen Wang
  • Yaru Lian
  • Bin Guo
  • Miao Han
  • Xiaoe Zhang
  • Xiaoting Zhu
  • Sixian Xu
  • Zengli Guo
  • Yunli Bi
  • Qian Shen
  • Xiang Wang
  • Jiaojiao Liu
  • Yuan Zhuang
  • Ting Ni
  • Hong Xu
  • Xiaohui Wu
چکیده

Congenital anomalies of the kidney and urinary tract (CAKUT) are among the most common developmental defects in humans. Despite of several known CAKUT-related loci (HNF1B, PAX2, EYA1, etc.), the genetic etiology of CAKUT remains to be elucidated for most patients. In this study, we report that disruption of the Holliday Junction resolvase gene Gen1 leads to renal agenesis, duplex kidney, hydronephrosis, and vesicoureteral reflux (VUR) in mice. GEN1 interacts with SIX1 and enhances the transcriptional activity of SIX1/EYA1, a key regulatory complex of the GDNF morphogen. Gen1 mutation impairs Grem1 and Gdnf expression, resulting in excessive ureteric bud formation and defective ureteric bud branching during early kidney development. These results revealed an unidentified role of GEN1 in kidney development and suggested its contribution to CAKUT.

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عنوان ژورنال:

دوره 14  شماره 

صفحات  -

تاریخ انتشار 2018