Large deletion of Wdr19 in developing renal tubules disrupts primary ciliogenesis, leading to polycystic kidney disease in mice

Shang Shiuan Yu, Ellian Wang, Chih Ying Chiang, Po Hao Cheng, Yu Shan Yeh, Ying Ying Wu, Yuan Yow Chiou, Si Tse Jiang

研究成果: Article同行評審

1 引文 斯高帕斯(Scopus)

摘要

WD repeat domain 19 (Wdr19) is a major component of the intraflagellar transport (IFT) machinery, which is involved in the function of primary cilia. However, the effects of Wdr19 on primary cilia formation, cystogenesis, and polycystic kidney disease (PKD) progression remain unclear. To study these effects, we generated three lines of kidney-specific conditional knockout mice: Wdr19-knockout (Wdr19-KO, Wdr19f/−::Cdh16-CreTg/0), Pkd1-knockout (Pkd1-KO, Pkd1f/−::Cdh16-CreTg/0), and Wdr19/Pkd1-double knockout (Wdr19&Pkd1-dKO, Wdr19f/−;Pkd1f/−::Cdh16-CreTg/0) mice. Ultrastructural analysis using transmission electron microscopy (TEM) indicated that the primary cilia were almost absent at postnatal day 10 in Wdr19-KO mice compared with Pkd1-KO and wild-type (WT) mice. However, the primary cilia appeared structurally normal even if malfunctional in Pkd1-deficient cysts. The Pkd1-KO mice had the most severe PKD progression, including the shortest lifespan (14 days) and the largest renal cysts, among the three knockout lines. Thus, the molecular mechanism of renal cystogenesis in Wdr19-KO mice (primary cilia abrogation) was different from that in Pkd1-KO mice (primary cilia malfunction). In summary, Wdr19 deficiency leads to primary cilia abrogation and renal cyst formation. Wdr19 is primarily proposed to participate in retrograde IFT and to be crucial for the construction of primary cilia, which are critical organelles for tubulogenesis in the developing kidneys.

原文English
頁(從 - 到)5-16
頁數12
期刊Journal of Pathology
257
發行號1
DOIs
出版狀態Published - 2022 5月

All Science Journal Classification (ASJC) codes

  • 病理學與法醫學

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