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Updated: Feb 12, 2026

A Possible Zebrafish Model of Polycystic Kidney Disease: Knockdown of wnt5a Causes Cysts in Zebrafish Kidneys

A Possible Zebrafish Model of Polycystic Kidney Disease: Knockdown of wnt5a Causes Cysts in Zebrafish Kidneys

Published on: December 2, 2014

常染色体優性多発性嚢胞腎疾患（ADPKD）の原因となるポリシスチン-1（PC1）バリアントによるポリシスチン繊毛局在およびチャネル機能の破壊

Kotdaji Ha¹, Gabriel B Loeb^2,3, Meyeon Park²

¹Department of Physiology, University of California, San Francisco, San Francisco, CA, USA.

Journal of the American Society of Nephrology : JASN

|February 10, 2026

要旨

Background:

Autosomal dominant polycystic kidney disease (ADPKD) is the leading monogenic cause of kidney failure and affects millions of people worldwide. Despite the prevalence of ADPKD, limited mechanistic understanding has hindered therapeutic development. Most ADPKD is caused by loss of function variants in Polycystin-1 (PC1).

Methods:

We developed assays that quantify the effect of nontruncating variants on PC1 ciliary localization, membrane trafficking, and Polycystin channel function.

Results:

We evaluated 29 nontruncating variants in PC1 and found that pathogenic variants disrupt two molecular phenotypes: 1) localization of PC1 at the primary cilium or 2) Polycystin ion channel activity. Ciliary localization of a subset of Polycystin variants was restored when cells were cultured at low temperature. A subset of variants with localization restored by low temperature formed functional channels.

Conclusions:

This study demonstrated that disruptions in Polycystin ciliary trafficking and channel function are common causes of ADPKD. Defects in ciliary trafficking and channel function can be rescued for a subset of pathogenic variants, establishing a foundation for Polycystin-targeted therapies in ADPKD.

キーワード:

常染色体優性多発性嚢胞腎疾患ポリシスチン-1 繊毛イオンチャネル遺伝子変異腎疾患治療法開発

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Spectral Karyotyping to Study Chromosome Abnormalities in Humans and Mice with Polycystic Kidney Disease

Spectral Karyotyping to Study Chromosome Abnormalities in Humans and Mice with Polycystic Kidney Disease

Published on: February 3, 2012

Use of Ultra-high Field MRI in Small Rodent Models of Polycystic Kidney Disease for In Vivo Phenotyping and Drug Monitoring

Use of Ultra-high Field MRI in Small Rodent Models of Polycystic Kidney Disease for In Vivo Phenotyping and Drug Monitoring

Published on: June 23, 2015

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