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

doi:10.1002/path.5863

journal article Feb 15, 2022

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

The Journal of Pathology Vol. 257 No. 1 pp. 5-16 · Wiley

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Abstract

AbstractWD 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. © 2022 The Pathological Society of Great Britain and Ireland.

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Details

Published: Feb 15, 2022
Vol/Issue: 257(1)
Pages: 5-16
License: View

Authors

S

Shang‐Shiuan Yu

Institute of Clinical Medicine, College of Medicine National Cheng Kung University Tainan Taiwan; National Laboratory Animal Center National Applied Research Laboratories Tainan Taiwan

E

Ellian Wang

Department of Physiology National Cheng Kung University Medical College Tainan Taiwan

C

Chih‐Ying Chiang